19109OCT2014

CNO Report 191

Release Date 10 OCT 2014

Draft Report Compiled by

Ralph Turchiano

http://www.clinicalnews.org

 

In this issue:

1. Healthy fats help diseased heart muscle process and use fuel
2. New way to detox? ‘Gold of Pleasure’ oilseed boosts liver detoxification enzymes
3. New ways to treat anemia could evolve from acetate supplement research
4. An apple a day could keep obesity away
5. Antioxidant found in grapes uncorks new targets for acne treatment
6. New article shows daily use of certain supplements can decrease health-care expenditures
7. Omega-3 fatty acids may prevent some forms of depression
8. Drug-food interactions in mountaineering
9. Lift weights, improve your memory
10. Several experiments on rats prove that chronic melatonine consumption fights obesity and diabetes
11. Vitamin D significantly improves symptoms of winter-related atopic dermatitis in children
12. ‘Virological penicillin’: Plant MIR2911 directly targets influenza A viruses
13. Oral chelation for environmental lead toxicity
14. Probiotics protect children and pregnant women against heavy metal poisoning
15. Sugar linked to memory problems in adolescent rats
16. Sleeping in dentures doubles the risk of pneumonia in the elderly
17. Grapefruit juice stems weight gain in mice fed a high-fat diet, study finds
18. Researchers identify a new class of ‘good’ fats
19. Drinking decaf coffee may be good for the liver

Healthy fats help diseased heart muscle process and use fuel

Oleate, a common dietary fat found in olive oil, restored proper metabolism of fuel in an animal model of heart failure.

The findings are reported in the journal Circulation by researchers at University of Illinois at Chicago College of Medicine.

Heart failure affects nearly 5 million Americans, and more than half a million new cases are diagnosed each year. Heart failure is not the same as having a heart attack — it is a chronic disease state where the heart becomes enlarged, or hypertrophic, in response to chronic high blood pressure which requires it to work harder to pump blood. As the heart walls grow thick, the volume of blood pumped out diminishes and can no longer supply the body with enough nutrients.

Failing hearts are also unable to properly process or store the fats they use for fuel, which are contained within tiny droplets called lipid bodies in heart muscle cells. The inability to use fats, the heart’s primary fuel source, causes the muscle to become starved for energy. Fats failing hearts manage to metabolize break down into toxic intermediary by-products that further contribute to heart disease.

Lewandowski and his colleagues looked at how healthy and failing intact, beating rat hearts reacted to being supplied with either oleate or palmitate, a fat associated with the Western diet and found in dairy products, animal fats and palm oil.

When the researchers perfused failing rat hearts with oleate, “we saw an immediate improvement in how the hearts contracted and pumped blood,” said E. Douglas Lewandowski, director of the UIC Center for Cardiovascular Research and senior and corresponding author on the study.

Lewandowski and colleagues tracked the location of fat molecules in the cells of the diseased hearts by tagging them with a nonradioactive heavy isotope of carbon, which is detected using magnetic resonance spectroscopy. This technology allows researchers to watch biochemical reactions, like metabolism, as they occur in real-time in functioning organs. Using this technique, Lewandowski noticed that the metabolism of fats within the cardiac cells of these hearts became normalized.

In contrast, when the researchers perfused the diseased hearts with palmitate, fat metabolism was imbalanced, and cells struggled to access fuel. There was also a rise in toxic fatty byproducts — another consequence of dysregulated fat metabolism.

In addition to balancing fat metabolism and reducing toxic fat metabolites in hypertrophic hearts, Lewandowski said, oleate also restored the activation of several genes for enzymes that metabolize fat.

“These genes are often suppressed in hypertrophic hearts,” he said. “So the fact that we can restore beneficial gene expression, as well as more balanced fat metabolism, plus reduce toxic fat metabolites, just by supplying hearts with oleate – a common dietary fat — is a very exciting finding.”

“This gives more proof to the idea that consuming healthy fats like oleate can have a significantly positive effect on cardiac health,” Lewandowski said — even after disease has begun.

 

 

New way to detox? ‘Gold of Pleasure’ oilseed boosts liver detoxification enzymes

URBANA, Ill. – University of Illinois scientists have found compounds that boost liver detoxification enzymes nearly fivefold, and they’ve found them in a pretty unlikely place—the crushed seeds left after oil extraction from an oilseed crop used in jet fuel.

“The bioactive compounds in Camelina sativa seed, also known as Gold of Pleasure, are a mixture of phytochemicals that work together synergistically far better than they do alone. The seed meal is a promising nutritional supplement because its bioactive ingredients increase the liver’s ability to clear foreign chemicals and oxidative products. And that gives it potential anti-cancer benefit,” said Elizabeth Jeffery, a U of I professor of nutritional toxicology.

Oilseed crops, including rapeseed, canola, and camelina, contain some of the same bioactive ingredients—namely, glucosinolates and flavonoids—found in broccoli and other cruciferous vegetables and in nearly the same quantities, she noted.

Because the oil from oilseed crops makes an environmentally friendly biofuel, scientists have been hoping to find a green use for the protein-rich seed meal left after oil extraction. Animal feed was the obvious choice, but there were a couple of problems. Some rapeseed glucosinolates are toxic, and producers have balked at paying Canada for canola seed, the low-glucosinolate rapeseed that country had developed.

Jeffery thought Camelina sativa was worth a look so she began to work with USDA scientist Mark Berhow. In the first study of camelina’s bioactive properties, Berhow isolated four major components—three glucosinolates and the flavonoid quercetin—from its defatted seed meal.

Back at Jeffery’s U of I lab, researchers began to test these components on mouse liver cells both individually and together. They found that all four major camelina bioactives induced the detoxifying liver enzyme NQO1 when they were used alone. However, when a particular glucosinolate, GSL9, was paired with the flavonoid quercetin, there was a synergistic effect.

“When these two bioactives were combined, induction of the detoxifying liver enzyme increased nearly fivefold,” said Nilanjan Das, a postdoctoral student in Jeffery’s lab.

In all the experiments, the scientists used sulforaphane, the cancer-protective component of broccoli, as a control because it is known to induce NQO1, the detoxifying enzyme. Like camelina seed meal, broccoli contains the flavonoid quercetin, so they decided to look for synergy between sulforaphane and quercetin.

“As had been the case with camelina’s GSL9 and quercetin, the combined effect of quercetin and sulforaphane—in proportions found naturally in broccoli—was far greater than when either was used alone. This demonstrates to us the importance of eating whole foods. Thanks to synergy among its bioactive components, whole broccoli appears to be more powerful than purified sulforaphane that you might buy at a vitamin store or on the Internet,” Das said.

Nilanjan Das, Mark A. Berhow, Donato Angelina, and Elizabeth H. Jeffery are co-authors of “Camelina sativa Defatted Seed Meal Contains Both Alkyl Sulfinyl Glucosinolates and Quertecin that Synergize Bioactivity.” The article is available pre-publication online in the Journal of Agricultural and Food Chemistry. Funding was provided by USDA.

 

New ways to treat anemia could evolve from acetate supplement research

DALLAS – Sept. 29, 2014 – UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

“Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy,” said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.

Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.

“Our study shows that acetate functions as a biochemical ‘flare,’ linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway,” Dr. Garcia said.

An apple a day could keep obesity away

September 29, 2014

By Sylvia Kantor, College of Agricultural, Human & Natural Resource Sciences

PULLMAN, Wash. – Scientists at Washington State University have concluded that nondigestible compounds in apples – specifically, Granny Smith apples – may help prevent disorders associated with obesity. The study, thought to be the first to assess these compounds in apple cultivars grown in the Pacific Northwest, appears in October’s print edition of the journal Food Chemistry.

 

“We know that, in general, apples are a good source of these nondigestible compounds but there are differences in varieties,” said food scientist Giuliana Noratto, the study’s lead researcher. “Results from this study will help consumers to discriminate between apple varieties that can aid in the fight against obesity.”

 

The tart green Granny Smith apples benefit the growth of friendly bacteria in the colon due to their high content of non-digestible compounds, including dietary fiber and polyphenols, and low content of available carbohydrates. Despite being subjected to chewing, stomach acid and digestive enzymes, these compounds remain intact when they reach the colon. Once there, they are fermented by bacteria in the colon, which benefits the growth of friendly bacteria in the gut.

The study showed that Granny Smith apples surpass Braeburn, Fuji, Gala, Golden Delicious, McIntosh and Red Delicious in the amount of nondigestible compounds they contain.

 

“The nondigestible compounds in the Granny Smith apples actually changed the proportions of fecal bacteria from obese mice to be similar to that of lean mice,” Noratto said.

 

The discovery could help prevent some of the disorders associated with obesity such as low-grade, chronic inflammation that can lead to diabetes. The balance of bacterial communities in the colon of obese people is disturbed. This results in microbial byproducts that lead to inflammation and influence metabolic disorders associated with obesity, Noratto said.

 

“What determines the balance of bacteria in our colon is the food we consume,” she said.

Re-establishing a healthy balance of bacteria in the colon stabilizes metabolic processes that influence inflammation and the sensation of feeling satisfied, or satiety, she said.

 

The study was funded with an Emerging Research Issues Internal Competitive Grant from the Agricultural Research Center at Washington State University’s College of Agricultural, Human and Natural Resource Sciences.

 

 

Antioxidant found in grapes uncorks new targets for acne treatment

UCLA study points to resveratrol as key to possible combination therapy

Got grapes? UCLA researchers have demonstrated how resveratrol, an antioxidant derived from grapes and found in wine, works to inhibit growth of the bacteria that causes acne.

The team also found that combining resveratrol with a common acne medication, benzoyl peroxide, may enhance the drug’s ability to kill the bacteria and could translate into new treatments.

Published in the current online edition of the journal Dermatology and Therapy, the early lab findings demonstrated that resveratrol and benzoyl peroxide attack the acne bacteria, called Propionibacterium acnes, in different ways.

Resveratrol is the same substance that has prompted some doctors to recommend that adults drink red wine for its heart-health properties. The antioxidant stops the formation of free radicals, which cause cell and tissue damage. Benzoyl peroxide is an oxidant that works by creating free radicals that kill the acne bacteria.

“We initially thought that since actions of the two compounds are opposing, the combination should cancel the other out, but they didn’t,” said Dr. Emma Taylor, the study’s first author and an assistant clinical professor of medicine in the division of dermatology at the David Geffen School of Medicine at UCLA. “This study demonstrates that combining an oxidant and an antioxidant may enhance each other and help sustain bacteria-fighting activity over a longer period of time.”

The team grew colonies of the bacteria that causes acne and then added various concentrations of resveratrol and benzoyl peroxide both alone and together. The researchers monitored the cultures for bacterial growth or killing for 10 days.

They found that benzoyl peroxide was able to initially kill the bacteria at all concentration levels, but the effect was short lived and didn’t last beyond the first 24 hours.

Resveratrol didn’t have a strong killing capability, but it inhibited bacterial growth for a longer period of time. Surprisingly, the two compounds together proved the most effective in reducing bacteria counts.

“It was like combining the best of both worlds and offering a two-pronged attack on the bacteria,” said senior author Dr. Jenny Kim, professor of clinical medicine in the division of dermatology at the Geffen School.

Scientists have understood for years how benzoyl peroxide works to treat acne, but less has been known about what makes resveratrol effective — even though it has been the subject of previous studies. Using a high-powered microscope, the UCLA researchers observed that bacteria cells lost some of the structure and definition of their outer membranes, which indicated that resveratrol may work by altering and possibly weakening the structure of the bacteria.

The researchers also cultured human skin cells and blood cells with the two compounds to test their toxicity. They found that benzoyl peroxide was much more toxic than resveratrol, which could help explain what causes skin to become red and irritated when it’s used as a topical treatment in high dose or concentration.

Taylor noted that combining the two compounds allowed for prolonged antibacterial effects on the acne bacteria while minimizing its toxicity to other skin cells. The finding could lead to a more effective and less irritating topical acne therapy.

“We hope that our findings lead to a new class of acne therapies that center on antioxidants such as resveratrol,” Taylor said.

The next stage of research will involve further laboratory testing to better understand the mechanism of the two compounds. Additional research will be needed to validate the findings in patients.

Millions suffer from acne, and it has a significant psychosocial effect on patients, but limited progress has been made in developing new strategies for treating it. According to researchers, antibiotic resistance and side effects limit the efficacy of the current treatments, which include benzoyl peroxide, retinoids, antibiotics and Accutane (isotretinonin).

 

 

New article shows daily use of certain supplements can decrease health-care expenditures

Washington, D.C., October 1, 2014—Use of specific dietary supplements can have a positive effect on health care costs through avoided hospitalizations related to Coronary Heart Disease (CHD), according to a new article published in the Journal of Dietary Supplements(1). The article, “From Science to Finance—A Tool for Deriving Economic Implications from the Results of Dietary Supplement Clinical Studies,” published by Christopher Shanahan and Robert de Lorimier, Ph.D., explores a potential cost-benefit analysis tool that, when applied to a high-risk population (U.S. adults over 55 with CHD) who take dietary supplements, specifically omega-3 fatty acid or B vitamin dietary supplements, can result in the reduction of the individuals’ odds of experiencing a costly medical event.

Hospitalizations for all U.S. adults over the age of 55 with CHD cost the United States over $64 billion in 2012(2), and the amount spent on the treatment of CHD, rather than the prevention, is burdensome on both the societal and individual levels—and only expected to increase, according to the article. “One way to control the burden of CHD costs is to minimize the number of costly inpatient procedures,” the authors said. “Many dietary supplement products are available in the market today that have been shown to have positive effects on heart health through associated clinical studies…Thus, the potential decrease of total health care expenditures in the United States is a strong argument for the daily use of dietary supplements.”

According to the authors’ analysis of all U.S. adults over the age of 55 diagnosed with CHD:

• If every high-risk person in the target population were to take omega-3 supplements at preventive intake levels daily, there would be an average of $2.1 billion in avoided expenditures per year and a cumulative of $16.5 billion in avoided expenditures between 2013 – 2020
• If every high-risk person in the target population were to take B vitamins at preventive intake levels daily, there would be an average of $1.5 billion in avoided expenditures per year and a cumulative of $12.1 billion in avoided expenditures between 2013 – 2020

“This is a relatively low-technology, yet smart, approach that can be used by consumers, physicians, employers, and policymakers as a means to reduce personal and societal health care costs,” the authors concluded.

The cost-savings model presented in this article was first presented in a report, “Smart Prevention—Health Care Cost Savings Resulting from the Targeted Use of Dietary Supplements,” in which Frost & Sullivan conducted a systematic review of scientific research in peer-reviewed, published studies that looked separately at relationships between omega-3 supplement intake and the risk of a CHD-attributed event, and B vitamins intake and the risk of a CHD-attributed event. The firm then projected the rates of CHD-attributed medical events across U.S. men and women over the age of 55 with CHD and applied a cost benefit analysis to determine the cost savings if people in this targeted population took omega-3 supplements or B vitamin supplements at preventive intake levels. The report was funded through a grant from the CRN Foundation.

Omega-3 fatty acids may prevent some forms of depression

Reports new study in Biological Psychiatry

Reports new study in Biological Psychiatry

Philadelphia, PA, October 1, 2014

Patients with increased inflammation, including those receiving cytokines for medical treatment, have a greatly increased risk of depression. For example, a 6-month treatment course of interferon-alpha therapy for chronic hepatitis C virus infection causes depression in approximately 30% of patients.

Omega-3 fatty acids, more commonly known as fish oil, have a long list of health benefits, including lowering the risk of heart disease and reducing triglyceride levels. These nutritional compounds are also known to have anti-depressant and anti-inflammatory properties.

Despite some recent negative findings, as their tendency to increase the risk for prostate cancer was proven and some of the putative health benefits were not replicated in large trials, omega-3’s remain of high interest to the depression field, where several studies have suggested benefits for depression and other psychiatric disorders.

This led a group of international researchers, led by senior author Dr. Carmine Pariante, to conduct a randomized, double-blind, placebo-controlled study in order to carefully evaluate the effects of omega-3 fatty acids on inflammation-induced depression.

They recruited 152 patients with hepatitis C to participate, each of whom was randomized to receive two weeks of treatment with EPA, DHA, or placebo. EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) are the two main omega-3 fatty acids in fish oil supplements.

Following the two-week treatment, the patients received a 24-week course of interferon-alpha treatment and were evaluated repeatedly for depression.

The researchers found that treatment with EPA, but not DHA or placebo, decreased the incidence of interferon-alpha-induced depression in patients being treated for hepatitis C.

Pariante, a Professor at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London, added, “The study shows that even a short course (two weeks) of a nutritional supplement containing one such omega-3 polyunsaturated fatty acid (EPA) reduced the rates of new-onset depression to 10%.”

In addition, both EPA and DHA delayed the onset of depression, and both treatments were well tolerated, with no serious side effects.

“These new data provide promising support for omega-3 fatty acids to prevent depression, complementing other studies where omega-3’s were found to enhance antidepressant treatment,” said Dr. John Krystal, Editor of Biological Psychiatry.

EPA is considered an “endogenous” anti-inflammatory, and in previous work, also published in Biological Psychiatry, these same authors found that subjects with low levels of endogenous EPA in the blood were at higher risk of developing depression. Therefore, the authors speculate that this nutritional intervention restores the natural protective anti-inflammatory capabilities of the body, and thus protects patients from new-onset depression when inflammation occurs.

Although further work is still necessary and the findings must be replicated, these data indicate that omega-3 polyunsaturated fatty acids may be effective in preventing depression in a group of patients at high-risk of depression because of increased inflammation.

The article is “Omega-3 Fatty Acids in the Prevention of Interferon-Alpha-Induced Depression: Results from a Randomized, Controlled Trial” by Kuan-Pin Su, Hsueh-Chou Lai, Hui-Ting Yang, Wen-Pang Su, Cheng-Yuan Peng, Jane Pei-Chen Chang, Hui-Chih Chang, and Carmine M. Pariante (doi: 10.1016/j.biopsych.2014.01.008). The article appears in Biological Psychiatry, Volume 76, Issue 7 (October 1, 2014), published by Elsevier.

—

Drug-food interactions in mountaineering

 

Failure to carry out strict control of the products mountaineers consume could endanger their health

Climber taking the final few steps onto the 20,305 ft. (6,189 m) summit of Imja Tse (Island Peak) in Nepal.

UPV/EHU-University of the Basque Country researchers have studied the nutritional and health situations existing at high altitudes as well as the routinely used nutritional ergogenic and pharmacological aids.  According to their study, the possible interactions between drugs and food and nutrients taken may endanger the mountaineer’s health if all this is not conducted under strict control.

 

According to a recent paper published by the researchers Aritz Urdampilleta-Otegui, PhD in Physical Education and Sports and lecturer in the Department of Physical and Sports Education of the UPV/EHU-University of the Basque Country and at the Government of the Basque Autonomous Community (region), and Saioa Gómez-Zorita, PhD in Pharmacy and Food Sciences and researcher at the UPV/EHU’s Department of Pharmacy and Food Sciences, it is necessary to control the administering of drugs that interact with the foods consumed and which may be detrimental for the health of the mountaineer.

 

Among the main performance-limiting factors in mountaineering are muscle glycogen depletion and increased protein catabolism, hydroelectrolyte imbalance, and Acute Mountain Sickness (AMS). An optimum diet is essential for withstanding this situation of great stress experienced at high altitudes and stays in excess of three weeks. Even so, AMS in mountaineers is sometimes inevitable and in these cases drugs are used to tackle this situation, which if this is not done under strict control, the supplementing could endanger the health of the mountaineer owing to the potential interactions that could arise with the food or nutritional ergogenic aids consumed.

 

More and more tourists head to high mountains or participate in high-altitude trekking. Many of them have not had previous experience in high mountains. These stays lead to great changes in physiological terms like increased heart rate, increased systemic and pulmonary blood pressure, hyperventilation, fluid retention, decreased haemoglobin saturation (SaO2), among others. Owing to the difficulties involved in hypoxia, intense cold and doing exercise in conditions of little food, climbing up to high altitudes leads to routinely resorting to nutritional ergogenic aids or drugs. So updated information on the scientific evidence relating to pharmacological and nutritional ergogenic aids and potential interactions between them is of crucial importance.

 

Acute Mountain Sickness

At high altitudes, in particular above 4,000 metres and depending on individual susceptibility to hypoxy, it is normal for the appetite to diminish and for significant weight loss to occur. In particular, when one sleeps above 4,000 metres it is common to suffer from AMS, which is characterised by the onset of symptoms like headache, dizziness, nausea, insomnia, general fatigue and lack of appetite, among others. This appears in healthy mountaineers who climb high mountains. These symptoms typically develop during the first 6-10 hours of the ascent and register a peak on the second or third day of the stay. The incidence of AMS is variable but relatively high. At altitudes of between 4,000-5,800 metres 67% of the subjects are affected. Failure to properly control AMS can lead to cerebral oedema and risk of death. In this situation the mountaineer is no longer aware, is disoriented and does not coordinate properly, and this may lead to mistakes that could cause a serious accident.

 

The latest research suggests that preconditioning prior to ascent in intermittent hypoxy with a minimum of 12 sessions (2-4 sessions/week) undertaking aerobic-anerobic physical activity at above 4,000 metres helps to prevent AMS. Likewise, it has been shown that it is effective training for improving resilience in a range of sports.

 

The piece of work by the UPV/EHU researchers has studied the nutritional and health situations existing at high altitudes as well as the routinely used nutritional ergogenic and pharmacological aids.  After that, an assessment was made of the drug-food interactions that may arise, as well as the risks of these interactions for the health of mountaineers, and the following conclusions were reached:

– At high altitudes the seriousness of AMS affects the appetite and food intake of mountaineers.

– Particular attention needs to be paid to the use of drugs for AMS, as they could conceal the usual symptoms of AMS and, as a result, it is possible to go on climbing up until the moment when the body cannot become acclimatised to the altitude.

– Food supplements containing vitamin E before the stay and the taking of iron and vitamin C during the mountain-climbing activity is crucial.

– Isotonic beverages, glycerol, caffeine, aaR, omega 3 Fatty Acids and Ginkgo Biloba can be effective as nutritional ergogenic supplements.

– To tackle AMS, supplements (Ginkgo Biloba), diuretics, analgesics and, as a last resort, corticosteroids as well as immunomodulators are used. Acetazolamide has turned out to be the most effective drug for preventing AMS.

– In states of malnourishment, the interactions between nutrients and nutritional ergogenic aids and drugs can be greater, the most dangerous ones being the ones that take place between vasodilator supplements (omega 3, ginkgo biloba, garlic pearls, precursors of nitric oxide and acetyl salicylic acid).

– The mixing of diuretics (acetazolamide) with corticosteroids (prednisone or dexamethasone) is not recommended.

 

Lift weights, improve your memory

 

Study finds that one short bout of resistance exercise can enhance episodic memory

Posted September 30, 2014 | Atlanta, GA

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Here’s another reason why it’s a good idea to hit the gym: it can improve memory. A new Georgia Institute of Technology study shows that an intense workout of as little as 20 minutes can enhance episodic memory, also known as long-term memory for previous events, by about 10 percent in healthy young adults.

 

 

Another reason why it’s a good idea to hit the gym: it can improve memory. A new Georgia Institute of Technology study shows that an intense workout of as little as 20 minutes can enhance episodic memory, also known as long-term memory for previous events, by about 10 percent in healthy young adults.

The Georgia Tech research isn’t the first to find that exercise can improve memory. But the study, which was just published in the journal Acta Psychologica, took a few new approaches. While many existing studies have demonstrated that months of aerobic exercises such as running can improve memory, the current study had participants lift weights just once two days before testing them. The Georgia Tech researchers also had participants study events just before the exercise rather than after workout. They did this because of extensive animal research suggesting that the period after learning (or consolidation) is when the arousal or stress caused by exercise is most likely to benefit memory.

 

The study began with everyone looking at a series of 90 photos on a computer screen. The images were evenly split between positive (i.e. kids on a waterslide), negative (mutilated bodies) and neutral (clocks) pictures. Participants weren’t asked to try and remember the photos. Everyone then sat at a leg extension resistance exercise machine. Half of them extended and contracted each leg at their personal maximum effort 50 times. The control group simply sat in the chair and allowed the machine and the experimenter to move their legs. Throughout the process, each participant’s blood pressure and heart rate were monitored. Every person also contributed saliva samples so the team could detect levels of neurotransmitter markers linked to stress.

 

The participants returned to the lab 48 hours later and saw a series of 180 pictures – the 90 originals were mixed in with 90 new photos. The control group recalled about 50 percent of the photos from the first session. Those who exercised remembered about 60 percent.

 

“Our study indicates that people don’t have to dedicate large amounts of time to give their brain a boost,” said Lisa Weinberg, the Georgia Tech graduate student who led the project.

 

Although the study used weight exercises, Weinberg notes that resistance activities such as squats or knee bends would likely produce the same results. In other words, exercises that don’t require the person to be in good enough to shape to bike, run or participate in prolonged aerobic exercises.

 

While all participants remembered the positive and negative images better than the neutral images, this pattern was greatest in the exercise participants, who showed the highest physiological responses. The team expected that result, as existing research on memory indicates that people are more likely to remember emotional experiences especially after acute (short-term) stress.

 

But why does it work? Existing, non-Georgia Tech human research has linked memory enhancements to acute stress responses, usually from psychological stressors such as public speaking. Other studies have also tied specific hormonal and norepinephrine releases in rodent brains to better memory. Interestingly, the current study found that exercise participants had increased saliva measures of alpha amylase, a marker of central norepinephrine.

 

“Even without doing expensive fMRI scans, our results give us an idea of what areas of the brain might be supporting these exercise-induced memory benefits,” said Audrey Duarte, an associate professor in the School of Psychology. “The findings are encouraging because they are consistent with rodent literature that pinpoints exactly the parts of the brain that play a role in stress-induced memory benefits caused by exercise.”

 

The collaborative team of psychology and applied physiology faculty and students plans to expand the study in the future, now that the researchers know resistance exercise can enhance episodic memory in healthy young adults.

 

“We can now try to determine its applicability to other types of memories and the optimal type and amount of resistance exercise in various populations,” said Minoru Shinohara, an associate professor in the School of Applied Physiology. “This includes older adults and individuals with memory impairment.”

 

This research was supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award Program, National Institutes of Health, National Center for Research Resource

 

Several experiments on rats prove that chronic melatonine consumption fights obesity and diabetes

 

Scientists at the University of Granada also recommend to sleep in absolute darkness and avoid artificial illumination at night to avoid interference in the generation of endogenous melatonine.

 

Their research has been published in the last online issue of the prestigious Journal of Pineal Research

 

Scientists at the University of Granada, in collaboration with La Paz University Hospital in Madrid and the University of Texas, San Antonio in the US have demonstrated through several experiments conducted on Zucker obese rats that chronic consumption of melatonine helps combat obesity and diabetes mellitus type two.

 

Their research has confirmed that chronic administration of melatonine in young obese rats with diabetes mellitus type two, similar to its human equivalent, improves mitochondrial dysfunction (i.e. mitochondrial homeostatic functions) in a very efficient way, since it improves the consumption of oxygen, it diminishes the levels of free-radicals stress and prevents the destruction of the mitochondrial membrane.

 

These results, published in the last issue of the prestigious Journal of Pineal Research, confirm other similar studies conducted by these researchers during the last three years.

 

This research has been conducted by an interdisciplinary team from the Farmacology Department and the Neuroscience Institute, University of Granada, led by prof. Ahmad Agil, with the collaboration of Dr. Gumersindo Fernández, from the Endocrinology and Nutrition Service of La Paz University Hospital in Madrid, and prof. Russell Reiter, from the Structural Biology Department at the University of Texas, in San Antonio (USA)

 

According to the PI, prof. Ahmad Agil, both developed and developing countries currently evince a significant increase in obesity rates and also in diabetes type two. This increase results from a maladaptation of the human genome to modern environments, sedentary lifestyles, higher consumption of hypercaloric food and excessive exposure to artificial lightning, which reduce endogenous melatonine levels.

 

In the case of obesity, mitochondriae (our cells’ power stations) do not work properly (homeostatic imbalance) and their programmed destruction is thus accelerated (apoptosis). This leads to insuline resistance and the subsequent development of diabetes mellitus.

 

We must sleep in total darkness

 

In prof. Agil’s words, melatonine “is a natural substance present in plants, animals and humans; it works as a hormonal signal released during the night to establish circadian rhythms”

 

Currently this process is frequently interrupted, as a result of excessive exposure to artificial lightning during the night, which reduces the levels of endogenous melatonine—for instance, many people are in the habit of sleeping with their lamps, TVs or their computers switched on, or with the blinds drawn up. “For all these reasons, it is important to try to sleep in absolute darkness, to avoid interference in the generation of melatonine”.

 

Melatonine is a powerful antioxidant and anti-inflammatory: these properties constitute the foundation of its protective effect upon metabolism. ‘Melatonine is particularly abundant in vegetables, such as spices, herbs, tea, coffee, fruit, seeds and nuts. This is one of the main reasons why these sorts of food are particularly healthy’

 

General treatments with specific action upon adipose tissue, and in particular upon the mitochondria, and the increase in their efficiency, could have beneficial effects upon these sorts of diseases.

 

This study has been funded and supported by several projects from the Ministry of Economy and Competitiveness (Spain, Ref: SAF2013-45752), the GREIB MCI-International Excellence Campus of the Vice-rectorage of Research and Scientific Policy at the University of Granada, and the CTS-109 research group (Junta de Andalucía), Spain.

 

Vitamin D significantly improves symptoms of winter-related atopic dermatitis in children

A study conducted in more than 100 Mongolian schoolchildren found that daily treatment with a vitamin D supplement significantly reduced the symptoms of winter-related atopic dermatitis, a type of eczema. Led by a Massachusetts General Hospital (MGH) physician, the report in the October issue of theJournal of Allergy and Clinical Immunology supports the results of a preliminary study that showed similar results in a small group of children in Boston.

“While we don’t know the exact proportion of patients with atopic dermatitis whose symptoms worsen in the winter, the problem is common,” says Carlos Camargo, MD, DrPH, MGH Department of Emergency Medicine. “In this large group of patients, who probably had low levels of vitamin D, taking daily vitamin D supplements – which are inexpensive, safe and widely available – proved to be quite helpful.” Camargo led both the earlier Boston pilot study and the current investigation, which was performed in collaboration with investigators from the Health Sciences University of Mongolia.

A chronic inflammatory disorder of the skin, atopic dermatitis is uncomfortable and makes patients more vulnerable to bacterial infection. Symptoms of the disorder – most commonly seen in children – often worsen during wintertime. While controlled administration of ultraviolet light, which can stimulate the production of vitamin D in the skin, is a common treatment for severe atopic dermatitis, the possibility that vitamin D deficiency contributes to the seasonal worsening of symptoms had received little consideration prior to the Boston study. That investigation involved only 11 children but provided preliminary support for the hypothesis.

The current study, conducted in collaboration with the National Dermatology Center in Mongolia, enrolled 107 children, ages 2 to 17, from nine outpatient clinics in the capital city of Ulaanbaatar. The participants – all of whom had a history of atopic dermatitis symptoms worsening either during cold weather or around the transition from autumn to winter – were randomly divided into two groups. One group received a daily vitamin D dose of 1000 IU while the other received a placebo – both delivered in odorless, colorless and tasteless drops. Neither the children’s parents nor the study investigators knew to which group participants had been assigned.

Standard evaluations of atopic dermatitis symptoms were conducted at the outset of the trial and at the end of the month-long study period, and parents were also asked whether they saw any improvement in their child’s condition. At the end of the month, children receiving the vitamin D supplement had an average 29 percent improvement on the primary assessment tool used, compared with 16 percent improvement in the placebo group. Additional assessments – including the report from parents – also showed significantly greater improvement among children receiving vitamin D.

While data gathered at the outset of the study could not determine whether or not participating children were deficient in vitamin D, the authors note that an even larger study of Ulaanbaatar children conducted at the same time found significant vitamin D deficiency in 98 percent of participants, supporting the probability that the children in this study were also deficient. While future studies are needed to assess the value of vitamin D treatment in adults and in children with year-round symptoms, Camargo – a professor of Medicine at Harvard Medical School – says that parents of children with symptoms that worsen in the winter should try a vitamin D supplement for a few weeks when symptoms flare to see if it helps. He encourages parents to discuss this study and their plan with their primary care provider.

‘Virological penicillin’: Plant MIR2911 directly targets influenza A viruses

In a new study, Chen-Yu Zhang’s group at Nanjing University present an extremely novel finding that a plant microRNA, MIR2911, which is enriched in honeysuckle, directly targets influenza A viruses (IAV) including H1N1, H5N1 and H7N9. Drinking of honeysuckle soup can prevent IAV infection and reduce H5N1-induced mice death.

MicroRNAs (miRNAs) are a class of 19-24 nucleotide non-coding RNAs that do not encode for proteins. MiRNAs bind to target messenger RNAs to inhibit protein translation. In previous studies, the same group has demonstrated that stable miRNAs in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for disease and act as signaling molecules in intercellular communication. They have also reported that plant miRNAs can enter into the host blood and tissues via the route of food-intake. More importantly, once inside the host, the food-derived exogenous miRNAs can regulate host physiology by regulating host “target” genes.

Here, they report a surprising finding that MIR2911 from a Chinese herb honeysuckle can suppress IAV infection. Firstly, MIR2911 was found to be selectively retained in the boiled decoction of honeysuckle, and to be delivered into mouse plasma and lung tissue after drinking honeysuckle decoction. Then, the authors showed that MIR2911 represses various influenza viruses by targeting PB2 and NS1, two genes that are known to be required for influenza viral replication. Moreover, both synthetic MIR2911 and endogenous MIR2911 in honeysuckle decoction showed effective protection of animals from H1N1 infection, while such protection is dependent on the MIR2911-binding sites in the PB2 or NS1 genes. Last, MIR2911 is also effective to suppress the replication of influenza viruses H5N1 and H7N9, indicating a broad-spectrum anti-IAV effect of MIR2911.

This work is important for the following reasons:

1. It identifies MIR2911 as the first, active component directly targeting influenza A virus (IAVs). It is well known that Spanish Flu (H1N1) caused about 50 million people death. Recently reported mortality cases of pathogenic IAVs, such as H5N1 and H7N9 highlight the threat that these viruses pose to public health. Due to the rapid mutation and evolution of IAVs, it is almost impossible to prevent or cure the IAV infection by the same treatment. It is thus urgently to explore novel therapeutic strategy. With this in mind, plant MIR2911 is an ideal reagent for suppressing IAV infection, and it is fully expected that MIR2911, as well as MIR2911-enriched honeysuckle decoction, will be widely used for treatment of IAVs infection.
2. It is the first demonstration that a natural product can directly target virus. Since Fleming discovered penicillin nearly a century ago, antibiotics have been developed to target various bacterial infections and have saved the lives of millions of people. Unfortunately, no natural product that is effective against viral infection has been identified so far. As the first natural product directly targeting different IAVs, plant MIR2911 not only is the first active component identified in Traditional Chinese Medicine that directly targets various IAVs, but also may represent a novel type of natural product that effectively and directly suppresses viral infection. Furthermore, one of their ongoing studies shows that MIR2911 also directly targets Ebola virus, which is pandemic in West Africa and is becoming a crisis of public health. Thus, MIR2911 is able to serve as the “virological penicillin” to directly target various viruses.
3. Physiological concentration of MIR2911 in honeysuckle decoction sufficiently targets IAVs. For thousand years, Chinese have been drinking honeysuckle (also termed Lonicera japonica) decoction to treat influenza viral infections and the results show that honeysuckle decoction has a broad-spectrum anti-viral activity. It makes much easier and simpler to clinical usage by drinking honeysuckle tea/decoction. These results also provide another evidence to prove their previous discovery that dietary exogenous miRNAs are able to be functionally absorbed by mammalian gastrointestinal tract and play an important regulatory role in a cross-kingdom manner.
4. It further supports that exogenous small RNA via the route of food-intake can be delivered into host tissues with sufficient functional concentration. Peak level of MIR2911 in mouse lungs after administration honeysuckle soup is 2.6× 10-5 fmol (equivalent to 15600 copies) per 100 pg of total RNA. Given that about 70 μg total RNA can be extracted from 35 mg mouse lung tissues, and each mouse lung weighs approximate 0.12 g and contains 110-120 million cells, MIR2911 is estimated about 300~400 copies per cell. Another quantification approach by normalizing to U6 snRNA reveals that copy number of MIR2911 is even higher. Previous report has shown there are in average 400,000 copies of U6 snRNA per cell. Peak level of MIR2911 is about 250-fold less than U6 snRNA. Thus, there are about 1600 copies of MIR2911 in each lung cell. The quantification of MIR2911 is consistent with their previous study that MIR168a were present in mouse liver at approximate 800 copies per cell after feeding mice with fresh rice.

Oral chelation for environmental lead toxicity

Treatment with dimercaptosuccinic acid (DMSA), an oral chelation agent, was linked to reductions in the amount of lead in blood in young children in Zamfara State, Nigeria following environmental lead contamination, according to a study by Jane Greig and colleagues from Médecins Sans Frontières (MSF) published in this week’s PLOS Medicine.

The researchers report findings from an MSF program initiated in May 2010 to reduce lead poisoning in children following widespread environmental lead contamination due to gold mining in Zamfara State, Nigeria, leading to the death of an estimated 400 young children in the 3 months before chelation therapy was provided. The analysis included 3180 courses of DSMA chelation therapy administered between 1 June 2010 and 30 June 2011 to 1,156 children ≤5 y of age who had measurements of venous blood lead levels before and after each course of DMSA. The researchers found that, on average, treatment with DSMA was associated with a reduction in venous blood lead levels to 74.5% of the level at the start of the DMSA course. Nine of these 1,156 children died during the period studied, with lead poisoning likely involved in three of these deaths. The researchers report that no clinically severe adverse effects related to DMSA were seen during the study period, and no laboratory findings were recorded that required treatment discontinuation.

While the findings cannot be used to reach any definitive conclusions about the effectiveness or safety of oral DMSA as a treatment for lead poisoning in young children, blood lead levels decreased and the number of deaths was substantially reduced after the program was initiated.

The authors say: “This experience with basic supportive care and chelation in a large paediatric cohort adds significantly to the evidence base for clinical management of epidemic lead poisoning, particularly in resource-poor settings.”

Probiotics protect children and pregnant women against heavy metal poisoning

WASHINGTON, DC – October 7, 2014 — Yogurt containing probiotic bacteria successfully protected children and pregnant women against heavy metal exposure in a recent study. Working with funding from the Bill and Melinda Gates Foundation, Canadian and Tanzanian researchers created and distributed a special yogurt containing Lactobacillus rhamnosus bacteria and observed the outcomes against a control group. The work is published this week in mBio, the online open-access journal of the American Society for Microbiology.

A research team from the Canadian Centre for Human Microbiome and Probiotics, led by Dr. Gregor Reid, studied how microbes could protect against environmental health damage in poor parts of the world. Their lab research indicated that L. rhamnosus had a great affinity for binding toxic heavy metals. Working with this knowledge, the team hypothesized that regularly consuming this probiotic strain could prevent metals from being absorbed from the diet.

Working with the Western Heads East organization, Dr. Reid had already established a network of community kitchens in Mwanza, Tanzania to produce a probiotic yogurt for the local population. Mwanza is located on the shores of Lake Victoria, which is known to be polluted with pesticides and toxic metals including mercury. The team utilized this network to produce and distribute a new type of yogurt containing L. rhamnosus. The special yogurt was distributed to a group of pregnant women and a group of children. The researchers measured the baseline and post-yogurt levels of toxic metals.

The team found a significant protective effect of the probiotic against mercury and arsenic in the pregnant women. This is important as “reduction in these compounds in the mothers could presumably decrease negative developmental effects in their fetus and newborns,” according to Dr. Reid. While the results obtained in the children studied showed benefits and lower toxin levels, the sample size and duration of treatment did not allow statistical significance.

The researchers were excited by the potential of basic foodstuffs to provide preventative protection for pregnant women worldwide. They are currently investigating lactobacilli with higher and even more specific mechanisms of sequestering mercury.

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mBio is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.

The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM’s mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.

Sugar linked to memory problems in adolescent rats

Sugar consumption led to memory problems and brain inflammation

Studying rats as model subjects, scientists found that adolescents were at an increased risk of suffering negative health effects from sugar-sweetened beverage consumption.

Adolescent rats that freely consumed large quantities of liquid solutions containing sugar or high-fructose corn syrup (HFCS) in concentrations comparable to popular sugar-sweetened beverages experienced memory problems and brain inflammation, and became pre-diabetic, according to a new study from USC. Neither adult rats fed the sugary drinks nor adolescent rats who did not consume sugar had the same issues.

“The brain is especially vulnerable to dietary influences during critical periods of development, like adolescence,” said Scott Kanoski, corresponding author of the study and an assistant professor at the USC Dornsife College of Letters, Arts and Sciences.

Kanoski collaborated with USC’s Ted Hsu, Vaibhav Konanur, Lilly Taing, Ryan Usui, Brandon Kayser, and Michael Goran. Their study, which tested a total of 76 rats, was published online by the journal Hippocampus on Sept. 23.

About 35 to 40 percent of the rats’ caloric intake was from sugar or HFCS. For comparason, added sugars make up about 17 percent of the total caloric intake of teens in the U.S. on average, according to the CDC.

The rats were then tested in mazes that probe their spatial memory ability. Adolescent rats that had consumed the sugary beverages, particularly HFCS, performed worse on the test than any other group – which may be the result of the neuroinflammation detected in the hippocampus, Kanoski said.

The hippocampus is a part of the temporal lobe located deep within the brain that controls memory formation. People with Alzheimer’s Disease and other dementias often suffer damage to the hippocampus.

“Consuming a diet high in added sugars not only can lead to weight gain and metabolic disturbances, but can also negatively impact our neural functioning and cognitive ability.” Kanoski said. Next, Kanoski and his team plant to see how different monosaccharides (simple sugars) and HFCS affect the brain.

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This research was funded by USC institutional support.

 

Sleeping in dentures doubles the risk of pneumonia in the elderly

Alexandria, Va., USA – Poor oral health and hygiene are increasingly recognized as major risk factors for pneumonia among the elderly. To identify modifiable oral health-related risk factors, lead researcher Toshimitsu Iinuma, Nihon University School of Dentistry, Japan, and a team of researchers prospectively investigated associations between a constellation of oral health behaviors and incidences of pneumonia in the community-living of elders 85 years of age or older. This study, titled “Denture Wearing During Sleep Doubles the Risk of Pneumonia in Very Elderly,” has been published by the International and American Associations for Dental Research (IADR/AADR in the OnlineFirst portion of the Journal of Dental Research (JDR).

At baseline, 524 randomly selected seniors (228 males, 296 females, average age was 87.8 years old) were examined for oral health status and oral hygiene behaviors as well as medical assessment, including blood chemistry analysis, and followed up annually until first hospitalization for or death from pneumonia. Over a three-year follow-up period, 48 events associated with pneumonia were identified (20 deaths and 28 acute hospitalizations). Among 453 denture wearers, 186 (40.8%) who wore their dentures during sleep, were at higher risk for pneumonia than those who removed their dentures at night.

In a multivariate Cox model, both perceived swallowing difficulties and overnight denture wearing were independently associated with approximately 2.3-fold higher risk of the incidence of pneumonia, which was comparable with the high risk attributable to cognitive impairment, history of stroke and respiratory disease. In addition, those who wore dentures while sleeping were more likely to have tongue and denture plaque, gum inflammation, positive culture for Candida albicans, and higher levels of circulating interleukin-6 as compared to their counterparts.

This study provides empirical evidence that denture wearing during sleep is associated not only with oral inflammatory and microbial burden but also with incident pneumonia, suggesting potential implications of oral hygiene programs for pneumonia prevention in the community. Frauke Mueller, University of Geneva, Switzerland, wrote a perspective titled “Oral Hygiene Reduces the Mortality From Aspiration Pneumonia in Frail Elders,” commenting that these findings lead to a simple and straight forward clinical recommendation—denture wearing during the night should be discouraged in geriatric patients.

 

 

Grapefruit juice stems weight gain in mice fed a high-fat diet, study finds

Berkeley — Fad diets come and go, but might there be something to the ones that involve consuming grapefruit and grapefruit juice? New research at the University of California, Berkeley, suggests that a closer look at grapefruit juice is warranted.

A new study, to be published Wednesday, Oct. 8, in the peer-reviewed journal PLOS ONE, found that mice fed a high-fat diet gained 18 percent less weight when they drank clarified, no-pulp grapefruit juice compared with a control group of mice that drank water. Juice-drinking mice also showed improved levels of glucose, insulin and a type of fat called triacylglycerol compared with their water-drinking counterparts.

If these findings sound somewhat familiar, it may be because the link between grapefruit juice and weight loss – or just decreased weight gain – has been touted in Hollywood diets before. However, the earlier studies behind those claims were often small, not well-controlled and contradictory, according to Andreas Stahl and Joseph Napoli, the two UC Berkeley faculty members who led the new research.

This latest work was funded by the California Grapefruit Growers Cooperative, but the UC Berkeley researchers emphasized that the funders had no control or influence over the study design or research findings. Both Stahl and Napoli said they went into this research with some skepticism.

“I was surprised by the findings,” said Stahl, associate professor of nutritional sciences and toxicology. “We even re-checked the calibration of our glucose sensors, and we got the same results over and over again.”

Napolli added that “we see all sorts of scams about nutrition. But these results, based on controlled experiments, warrant further study of the potential health-promoting properties of grapefruit juice.”

Pitting juice against water

The study authors randomly divided mice into six groups, including a control group that drank only water. Those drinking grapefruit juice got a mixture diluted with water at different concentrations, and sweetened slightly with saccharin to counteract grapefruit’s bitterness. The researchers also added glucose and artificial sweeteners to the control group’s water so that it would match the calorie and saccharin content of the grapefruit juice.

At the end of the study period, the mice that ate the high-fat diet and drank diluted grapefruit juice not only gained less weight than their control counterparts, they also had a 13 to 17 percent decrease in blood glucose levels and a threefold decrease in insulin levels, which reveals greater sensitivity to insulin. (In Type 2 diabetes, the pancreas makes extra insulin to compensate for increased resistance to the hormone.)

The researchers gave one group of mice naringin, a bioactive compound in grapefruit juice that has been identified as a key agent in weight loss, and another group metformin, a glucose-lowering drug often prescribed for those with Type 2 diabetes.

The mice were fed a diet that was either 60 percent fat or 10 percent fat for 100 days, and their metabolic health was monitored throughout the study.

“The grapefruit juice lowered blood glucose to the same degree as metformin,” said Napoli, professor and chair of nutritional sciences and toxicology. “That means a natural fruit drink lowered glucose levels as effectively as a prescription drug.”

Weight effects only seen in high-fat diet

The group of high-fat-diet mice that received naringin had lower blood glucose levels than the control group, but there was no effect on weight, suggesting that some other ingredient in grapefruit juice is also beneficial.

“There are many active compounds in grapefruit juice, and we don’t always understand how all those compounds work,” said Stahl.

The study did not find as big an impact on mice that ate a low-fat diet. Those that drank the grapefruit juice saw a two-fold decrease in insulin levels, but there was no significant change in weight or other metabolic variables.

“The effects were more subtle for the low-fat diet group,” explained Stahl. “Mice are incredibly healthy animals with naturally low levels of bad cholesterol. So if they are eating a healthy, low-fat diet, it will take more to see a significant effect on their health.”

The researchers said they ruled out the typical explanations for weight loss in their study. It wasn’t the amount of food consumed, since the ingested calories among the different groups were about the same. The level of activity and body temperatures were comparable, and the authors even checked the calories eliminated in the feces of the mice to check for problems with the body’s absorption of nutrients.

“Basically, we couldn’t see a smoking gun that could explain why or how grapefruit juice affects weight gain,” said Stahl.

The researchers said they hope to continue the investigation into grapefruit juice. “Obesity and insulin resistance are such huge problems in our society, ” said Stahl. “These data provide impetus to carry out more studies.”

Researchers identify a new class of ‘good’ fats

Discovery offers a promising new direction for diabetes prevention and treatment

BOSTON – The surprising discovery of a previously unidentified class of lipid molecules that enhance insulin sensitivity and blood sugar control offers a promising new avenue for the prevention and treatment of type 2 diabetes.

The new findings, made by a team of scientists from Beth Israel Deaconess Medical Center (BIDMC) and the Salk Institute, are described in the October 9 online issue of the journal Cell.

“We were blown away to discover this completely new class of molecules,” says senior author Barbara Kahn, MD, Vice Chair of the Department of Medicine at BIDMC and the George R. Minot Professor of Medicine at Harvard Medical School. Named fatty acid hydroxyl fatty acids, or FAHFAs, these new molecules are in fat cells as well as other cells throughout the body. They now join a small group of fatty acids known to benefit health, which also include omega-3 fatty acids found in fish oil.

“Based on their biology, we can add FAHFAs to the small list of beneficial lipids,” says co-senior author Alan Saghatelian, PhD, a professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute in La Jolla, Calif. “These lipids are amazing because they can also reduce inflammation, suggesting that we might discover opportunities for these molecules in inflammatory diseases, such as Crohn’s disease and rheumatoid arthritis, as well as diabetes.”

Unlike omega-3 fatty acids, which are not made in mammals, FAHFAs are actually produced and broken down inside the human body. “This important feature gives FAHFAs an advantage in terms of therapeutic development because we can potentially modify the rate of production and breakdown throughout the body,” notes Kahn. “Because we can measure FAHFA levels in blood, low levels may turn out to be an early marker for the risk of developing type 2 diabetes. Consequently, if restoring FAHFA levels in insulin resistant individuals proves to be therapeutic, we may potentially be able to intervene before the development of frank diabetes.”

Glut-4 Mouse Model Is Key to Discovery

Key to the new findings was an animal model first created in the Kahn laboratory in the early 1990s. “Our adipose-specific GLUT-4 overexpressing mouse model [AG4OX] was initially designed after we observed that humans who are insulin resistant – and therefore more prone to develop diabetes and metabolic disease – have lower levels of the GLUT-4 glucose transporter molecules in their fat cells,” says Kahn. “To our surprise, overexpression of GLUT-4 in fat was sufficient to increase glucose tolerance and protect the mice against diabetes, even when the animals were obese.”

Over the years, the investigators have consistently observed that these mice have elevated fatty acids, which is generally associated with insulin resistance and glucose intolerance. But the AG4OX mice are sensitive to insulin and able to control blood sugar.

Therefore, to find out more about these fatty acids, Kahn collaborated with Saghatelian to conduct advanced lipodomic analyses of the AG4OX mice compared to normal littermates.

“Mass spectrometry lipodomics technology enables us to quantify hundreds of lipids from a biological sample by using the molecular weight of a lipid as a means to determine its presence in a cell or tissue,” explains Saghatelian. When the investigators examined the lipodomics results, they discovered a group of four lipids that were elevated 16-18-fold in the AG4OX mice, but not in the normal mice. A search of existing lipid databases to learn the identity (i.e. the structure) of these lipids turned up empty, so the investigators set out to further probe these mysterious molecules.

“Once we had the molecular formula from our lipodomics data, we knew that these lipids belonged to a novel family, and we were then able to use tandem mass spectrometry [MS/MS] and chemical synthesis to identify their structures,” explains Saghatelian. Through this approach, they discovered that the molecules consisted of a hydroxyl fatty acid and fatty acid that were joined by an ester bond.

“I’ve been conducting these analyses for more than a decade and FAHFA is one of only two new classes of lipids that we’ve uncovered,” he notes. “This is a rare discovery.”

The authors then went on to conduct a series of experiments. They discovered that feeding the mice extra FAHFAs resulted in a rapid and dramatic drop in blood sugar and rise in insulin. They also looked at FAHFA levels in human fat and plasma, studying samples from individuals who were known to be insulin resistant and at high risk for developing diabetes. In this case, FAHFA levels were found to be 50 to 75 percent lower than levels in people with normal insulin sensitivity, suggesting that changes in FAHFA levels might be contributing to diabetes.

The team also identified GPR-120, the cellular receptor that FAHFAs bind to. “When FAHFAs bind to GPR-120, they are able to control how much glucose is taken up into fat cells,” says Kahn. “The receptor may also be responsible for the effects of the novel lipids to reduce widespread macrophage activation, which is associated with obesity and with inflammatory diseases.

“The discovery of FAHFAs provides important new insights underlying metabolic and inflammatory diseases, and, of critical importance, offers viable new treatment avenues that we hope to be able to test in clinical trials,” says Kahn. “This is of critical importance as rates of obesity and type 2 diabetes remain at epidemic proportions worldwide.”

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School, and currently ranks third in National Institutes of Health funding among independent hospitals nationwide.

BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance, and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Senior Life and is a research partner of Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.

 

Drinking decaf coffee may be good for the liver

Researchers from the National Cancer Institute report that decaffeinated coffee drinking may benefit liver health. Results of the study published in Hepatology, a journal of the American Association for the Study of Liver Diseases, show that higher coffee consumption, regardless of caffeine content, was linked to lower levels of abnormal liver enzymes. This suggests that chemical compounds in coffee other than caffeine may help protect the liver.

Coffee consumption is highly prevalent with more than half of all Americans over 18 drinking on average three cups each day according to a 2010 report from the National Coffee Association. Moreover, the International Coffee Association reports that coffee consumption has increased one percent each year since the 1980s, increasing to two percent in recent years. Previous studies found that coffee consumption may help lower the risk of developing diabetes, cardiovascular disease, non-alcoholic fatty liver disease, cirrhosis, and liver cancer.

“Prior research found that drinking coffee may have a possible protective effect on the liver. However, the evidence is not clear if that benefit may extend to decaffeinated coffee,” explains lead researcher Dr. Qian Xiao from the National Cancer Institute in Bethesda, Maryland.

For the present study researchers used data from the U.S. National Health and Nutrition Examination Survey (NHANES, 1999-2010). The study population included 27,793 participants, 20 years of age or older, who provided coffee intake in a 24-hour period. The team measured blood levels of several markers of liver function, including aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transaminase (GGT) to determine liver health.

Participants who reported drinking three or more cups of coffee per day had lower levels of ALT, AST, ALP and GGT compared to those not consuming any coffee. Researchers also found low levels of these liver enzymes in participants drinking only decaffeinated coffee.

Dr. Xiao concludes, “Our findings link total and decaffeinated coffee intake to lower liver enzyme levels. These data suggest that ingredients in coffee, other than caffeine, may promote liver health. Further studies are needed to identify these components.”