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269 CNO 13 APR 2020

269CNO22MAR2020

In this Issue:

  1. University of Minnesota researchers discover Mediterranean diet ingredient may extend life
  2. Ethnobotanical medicine is effective against the bacterium causing Lyme disease
  3. The fat around your arteries may actually keep them healthy
  4. Researchers say extended antidepressant use creates physical dependence
  5. A nutraceutical formulation to fight hypertension
  6. New study indicates amino acid may be useful in treating ALS
  7. Tart cherry juice concentrate found to help improve endurance exercise performance
  8. People who eat a big breakfast may burn twice as many calories
  9. Recent research points the way toward a practical nutraceutical strategy for coping with RNA virus infections including influenza and coronavirus
  10. When should you eat to manage your weight? Breakfast, not late-night snacks
  11. Extra olive virgin oil keeps healthy properties when used for cooking
  12. Eat less, live longer
  13. Antioxidant precursor molecule could improve brain function in patients with MS
  14. Can’t sleep? Prebiotics could help
  15. Alzheimer’s: Can an amino acid help to restore memories?
  16. Low blood pressure linked to high mortality in older adults
  17. Gut bacteria can penetrate tumors and aid cancer therapy, study suggests
  18. Curcumin is the spice of life when delivered via tiny nanoparticles
  19. Consuming more olive oil associated with less heart disease in Americans
  20. Study shows low carb diet may prevent, reverse age-related effects within the brain
  21. Fish oil supplements linked to lower risk of heart disease and death
  22. Life expectancy crisis in the USA: The opioid crisis is not the decisive factor
  23. Analysis predicts purified fish oil could prevent thousands of cardiovascular events
  24. Too much salt weakens the immune system
  25. New study: Cannabis helps fight resistant bacteria
  26. Coconut oil reduces features of metabolic syndrome in obese females, animal study finds
  27. Researchers find that nicotinamide may help treat fibrotic eye diseases and mitigate vision loss
  28. Compound in fruit peels halts damage and spurs neuronal repair in multiple sclerosis
  29. Researchers suggest a special diet against asthma
  30. The Lancet Gasteroenterology & Hepatology: First clinical trial finds probiotic treatment with dead bacteria is better than placebo at alleviating symptoms of irritable bowel syndrome
  31. Treatment relieves depression in 90% of participants in small study

 

NEWS RELEASE 21-FEB-2020

University of Minnesota researchers discover Mediterranean diet ingredient may extend life

Newly published research shows olive oil in the diet may also help mitigate aging-related diseases

MINNEAPOLIS, MN- February 21, 2020 – Researchers at the University of Minnesota Medical School discover a potential new way in which diet influences aging-related diseases.

Doug Mashek, PhD, a professor in the Departments of Medicine and Biochemistry, Molecular Biology and Biophysics, leads a team of researchers who discovered that olive oil in the Mediterranean diet may hold the key to improving lifespan and mitigating aging-related diseases. Over the last eight years, with the help of multiple grants from the National Institutes of Health, their research findings were recently published in Molecular Cell.

Early studies on the diet suggested red wine was a major contributor to the health benefits of the Mediterranean diet because it contains a compound called resveratrol, which activated a certain pathway in cells known to increase lifespan and prevent aging-related diseases. However, work in Mashek’s lab suggests that it is the fat in olive oil, another component of the Mediterranean diet, that is actually activating this pathway.

According to Mashek, merely consuming olive oil is not enough to elicit all of the health benefits. His team’s studies suggest that when coupled with fasting, limiting caloric intake and exercising, the effects of consuming olive oil will be most pronounced.

“We found that the way this fat works is it first has to get stored in microscopic things called lipid droplets, which is how our cells store fat. And then, when the fat is broken down during exercising or fasting, for example, is when the signaling and beneficial effects are realized,” Mashek said.

The next steps for their research are to translate it to humans with the goal of discovering new drugs or to further tailor dietary regimens that improve health, both short-term and long-term.

“We want to understand the biology, and then translate it to humans, hopefully changing the paradigm of healthcare from someone going to eight different doctors to treat his or her eight different disorders,” Mashek said. “These are all aging-related diseases, so let’s treat aging.”

NEWS RELEASE 21-FEB-2020

Ethnobotanical medicine is effective against the bacterium causing Lyme disease

A preclinical study in test tubes showed that selected plant-based herbal medicines, especially Ghanaian quinine and Japanese knotweed, work better than antibiotics

FRONTIERS

Lyme disease, also called borreliosis, is the most common vector-borne disease in the Northern hemisphere. It is caused by the spirochete (corkscrew-shaped) bacterium Borrelia burgdorferi and close relatives and mainly spread through the bite of infected ticks.

Currently, more than 300,000 new cases are reported in the USA each year, compared to 65,000 in Europe, and these numbers are rising due to climate change and urban sprawl. The standard of care for Lyme disease, a course of antibiotics over 2-4 weeks, is not always effective: at least 10-20% of treated patients continue to experience symptoms after treatment. Late-stage Lyme patients may experience many different symptoms, including fatigue, joint pains, memory problems, facial paralysis, aches, stiffness in the neck, heart palpitations, and severe headaches. The discovery of novel treatments against Lyme disease is therefore of great interest.

In a new study published in Frontiers in Medicine, researchers from the Johns Hopkins Bloomberg School of Public Health, with colleagues at the California Center for Functional Medicine and Focus Health, surveyed the power of 14 plant-based extracts to kill Borrelia burgdorferi, compared to the currently used Lyme antibiotics doxycycline and cefuroxime.

The researchers tested these extracts’ effectiveness in vitro (outside of a living organism) against the free-swimming “planktonic” form of the bacterium as well as against microcolonies. Microcolonies are aggregates of bacteria, the first stage in the development of biofilms – structured bacterial communities that stick to a surface and are embedded in a slimy extracellular matrix.

The researchers show that plant extracts from black walnut, cat’s claw, sweet wormwood, Mediterranean rockrose, and Chinese skullcap had strong activity against B. burgdorferi, outperforming both tested antibiotics.

But by far the strongest performers were Ghanaian quinine (Cryptolepis sanguinolenta; also known as yellow-dye root, nibima, or kadze) and Japanese knotweed (Polygonum cuspidatum).

Ghanaian quinine is a shrub from West Africa containing the antimicrobial alkaloid cryptolepine, and is used in ethnomedicine to treat malaria, hepatitis, septicemia, and tuberculosis. Japanese knotweed is a traditional medicine in India and China that contains the polyphenol resveratrol. In other preclinical studies it has been found to have anti-tumor and anti-inflammatory effects and protect the nervous system and heart. Extracts from both plants were found to kill microcolonies of Borrelia burgdorferi and inhibit division of the planktonic form, even at low concentrations (0.03-0.5%). Remarkably, a single 7-day treatment with 1% Ghanaian quinine could completely eradicate the bacterium – it did not regrow, even under optimal conditions in the drug’s absence.

“This study provides the first convincing evidence that some of the herbs used by patients such as Cryptolepis, black walnut, sweet wormwood, cat’s claw, and Japanese knotweed have potent activity against Lyme disease bacteria, especially the dormant persister forms, which are not killed by the current Lyme antibiotics,” says Dr Ying Zhang from the Johns Hopkins Bloomberg School of Public Health.

“These findings are exciting as they offer opportunities for improved treatment of persistent Lyme disease, which is not helped by the current standard treatment. We are interested in further evaluating these potent herbal medicines through animal studies as well as clinical trials.”

However, not all tested compounds or herbs yielded positive results against the bacterium. Extracts of grapefruit seeds, green chiretta, ashwagandha, candy leaf (also known as stevia), fuller’s teasel, and Japanese teasel had little or no effect, and neither did the chemicals colloidal silver, monoglyceride monolaurin, or antimicrobial peptide LL37 from human immune cells. This was surprising, as anecdotal and preclinical studies suggested that they might be effective, and they are often used in the community of Lyme disease practitioners and patients.

“Many thousands of Lyme patients today, especially those with later-stage symptoms who have not been effectively treated, are in great need of efficacious, accessible treatment options,” says Dr Sunjya K. Schweig, CEO and co-Director of the California Center for Functional Medicine and Scientific Advisory Board Member of the Bay Area Lyme Foundation.

NEWS RELEASE 20-FEB-2020

The fat around your arteries may actually keep them healthy

MICHIGAN STATE UNIVERSITY

EAST LANSING, Mich. – A Michigan State University researcher is adding new evidence to the argument that the fat around our arteries may play an important role in keeping those blood vessels healthy.

The finding could affect how researchers test for treatments related to plaque buildup in our arteries, or atherosclerosis, an issue that can often lead to a heart attack, which is currently a leading cause of death in the United States.

The fat, known as perivascular adipose tissue, or PVAT, helps arteries do what scientists call “stress relax,” or let go of muscular tension while under constant strain. This is similar to the bladder, which expands to accommodate more liquid while at the same time keeping it from spilling out.

“In our study, PVAT reduced the tension that blood vessels experience when stretched,” said Stephanie Watts, MSU professor of pharmacology and toxicology in the College of Osteopathic Medicine. “And that’s a good thing, because the vessel then expends less energy. It’s not under as much stress.”

What made the finding so exciting, Watts said, whose study was recently published in the journal Scientific Reports, is that PVAT has largely been ignored by researchers who have thought its main job was to store lipids and do little more. Now her findings, built on previous results, could help redefine the way scientists view blood vessels.

Right now, scientists only divide blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media and the outermost layer called the tunica adventitia.

Watts would like scientists to recognize PVAT as the fourth layer, which others have called tunica adiposa – tunica means a membranous sheath enveloping or lining an organ and adiposa is a synonym for fat.

“For years, we ignored this layer – in the lab it was thrown out; in the clinic it wasn’t imaged. But now we’re discovering it may be integral to our blood vessels,” Watts said. “Our finding redefines what the functional blood vessels are and is part of what can be dysfunctional in diseases that afflict us, including hypertension. We need to pay attention to this layer of a blood vessel because it does far more than we originally thought.”

Other investigators have shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

But Watts and her colleagues wanted to test whether PVAT itself, rather than the substances it secretes, might play a role in how blood vessels perform. So, they decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

To do that, they tested the thoracic aorta in rats and found those with intact PVAT had more stress relaxation than those without.

“My mind was blown,” Watts said when she saw that the pieces with surrounding fat had measurably relaxed more than those without. “I made every single person in my lab come and look and I asked, ‘Tell me if I’m hallucinating…do you think this is real?'”

Watts and her colleagues also tested other arteries and were able to duplicate the same response.

“So, this tells us, it’s not just a one off,” Watts said. “It’s not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it’s a general phenomenon.”

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(Note for media: Please include a link to the original paper in online coverage: https://www.nature.com/articles/s41598-020-58368-x

Michigan State University has been working to advance the common good in uncommon ways for 160 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world’s most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges.

For MSU news on the Web, go to MSUToday. Follow MSU News on Twitter at twitter.com/MSUnews.

Contact: Stephanie Watts, College of Osteopathic Medicine: (517) 353-3724, wattss@msu.edu; Kim Ward, University Communications: (517) 432-0117, kward@msu.edu

NEWS RELEASE 20-FEB-2020

Researchers say extended antidepressant use creates physical dependence

Drug class ‘notoriously difficult to quit,’ yet not intended for permanent use, according to authors in the journal of the american osteopathic association

AMERICAN OSTEOPATHIC ASSOCIATION

 

CHICAGO–February 20, 2020–Patients who have taken antidepressants for years should consider coming off the medication. However, researchers say they will likely face difficult and even dangerous withdrawal symptoms due to a physical dependence.

The best process is to follow a tapering schedule while consulting with a physician, according to research in The Journal of the American Osteopathic Association. Stopping medication outright is almost never advisable.

“I understand that many people feel safe in that their depression or anxiety is continuously managed by medication. However, these are mind-altering drugs and were never intended as a permanent solution,” says Mireille Rizkalla, PhD, Assistant Professor, Department of Clinical Integration at Midwestern University Chicago College of Osteopathic Medicine, and lead author on this research. “Once the patient’s depression or anxiety has been resolved, the physician should guide them toward discontinuation, while providing non pharmacologic treatments to help them maintain their mental health.”

Hard to quit

Patients who stop taking their medication often experience Antidepressant Discontinuation Syndrome (ADS), which includes flulike symptoms, insomnia, nausea, imbalance, sensory disturbances often described as electric shocks or “brain zaps”, and hyperarousal.

Older, first-generation antidepressants often come with additional risks for more severe symptoms, including aggressiveness, catatonia, cognitive impairment, and psychosis. Discontinuing any antidepressant also carries a risk for gradual worsening or relapsing of depression and anxiety, as well as suicidal thoughts.

Indefinitely medicated

A recent report from the CDC said a quarter of people taking antidepressants had been using them for a decade or more. Rizkalla says this data makes the case that patients and physicians are overly reliant on medication without concern for long-term consequences.

“I think we have a real problem with patient care management, when it comes to prescribing antidepressants,” says Rizkalla. “We tend to put patients on an SSRI and more or less forget about them.”

She adds that, while relatively safe, antidepressants still carry side effects, including weight gain, sexual dysfunction and emotional numbing. She also urges caution as the evidence for antidepressant risk factors is based on short-term usage, and says there are no sufficient longitudinal studies on the neurologic impact of taking antidepressants for decades.

Rizkalla and her coauthors included the following tapering schedule for varying classes of antidepressants. However, she insists patients consult their physician before and throughout the process to monitor their symptoms and progress.

NEWS RELEASE 20-FEB-2020

A nutraceutical formulation to fight hypertension

Coupled with standard therapies, a combination of plant extracts improves cardiovascular health in hypertensive patients with poorly controlled blood pressure

ISTITUTO NEUROLOGICO MEDITERRANEO NEUROMED I.R.C.C.S.

SHARE PRINT E-MAILAdding a combination of three natural extracts to standard pharmacological treatments could help to fight hypertension, improving cardiovascular function especially in those patients whose blood pressure remains not well controlled. These are the conclusions of a study conducted by the Vascular Pathophysiology Laboratory of I.R.C.C.S. Neuromed in Pozzilli, in collaboration with the Medical University of Salerno, Federico II University in Naples, I.R.C.C.S. Multimedica in Milan, and Sapienza University of Rome. The findings were published in the Journal of the American Heart Association.

Extracts used in this nutraceutical formulation come from Bacopa Monnieri, Ginko biloba and green tea leaves, complexed with phosphatidylcholine, a natural phospholipid. Researchers evaluated its effects on a group of hypertensive patients, all of them receiving standard therapies. The main characteristic of the selected patients was that, despite pharmacological treatments, their blood pressure remained not well controlled.

“In a percentage of patients – explains Professor Carmine Vecchione, Dean of the Faculty of Medicine at Salerno University, director of the Unit of Cardiology at Ruggi D’Aragona Hospital in Salerno and Head of the Vascular Pathophysiology laboratory at I.R.C.C.S. Neuromed – blood pressure control, despite treatments, remains unsatisfactory. We also know that hypertensive state reduces tolerance to physical exercise, a parameter recognized as a valid indicator of the cardiovascular situation”.

In order to overcome this situation, researchers aimed to find an additional weapon in nutraceuticals. Selected patients, all of them receiving standard drug treatment, were divided into groups in order to test the efficacy of the plant extracts mix compared to placebo. Furthermore, experiments have been conducted, both on cellular and animal models, to highlight the biochemical mechanisms involved.

“We saw – says Dr. Albino Carrizzo, first author of the publication, researcher at I.R.C.C.S. Neuromed – that patients treated with this nutraceutical showed an improvement in crucial parameters such as oxygen consumption, strength, endurance to physical exercise. These are indicators of a more efficient endothelial function. Furthermore, cellular and animal models demonstrated that this effect is due to an increase of nitric oxide in the blood, an important element in vessels health. Finally, an interesting observation emerging from our research is that the four substances composing the mix have a hemodynamic action only when combined together, while they are ineffective when used individually. It is a real synergistic action”.

It is important to highlight that these results should not be seen as an alternative to standard therapies. “Hypertension is a very serious problem – concludes Vecchione – involving a growing part of the population and leading to serious pathologies. Patients must be aware that pharmacological treatments play a fundamental role in the management of the problem. If future researches will confirm our results, this new nutraceutical formulation will be a new weapon, accompanying standard therapies without replacing them”.

NEWS RELEASE 20-FEB-2020

New study indicates amino acid may be useful in treating ALS

Study published in Journal of Neuropathology & Experimental Neurology provides new model for ALS and its treatment

BRAIN CHEMISTRY LABS

(JACKSON, Wyo.- Feb. 20, 2020) – A naturally occurring amino acid is gaining increased attention from scientists as a possible treatment for ALS following a new study published today in the Journal of Neuropathology & Experimental Neurology. The study showed that the amino acid, L-serine, successfully reduced ALS-like changes in an animal model of ALS.

The scientists conducted the vervet study at the Behavioural Science Foundation, a specialized research facility on the Caribbean island of St. Kitts. After being exposed to a cyanobacterial neurotoxin called BMAA, the vervets developed aggregations of misfolded proteins similar to those seen in human ALS patients, and activated microglia, a type of immune cells, in their spinal cord and brain, similar to those that occur in the early stages of ALS. In contrast, vervets that also received the amino acid L-serine had significantly reduced ALS pathology.

Dr. David Davis at the Department of Neurology, University of Miami Miller School of Medicine who served as first author on the paper, said that the differences were profound. “Without L-serine co-administration, the BMAA-exposed vervets developed motor neuron degeneration, pro-inflammatory microglia and dense inclusions of TDP-43 and other misfolded proteins known to be associated with ALS,” Dr. Davis explained. “In animals dosed with L-serine, the progression of these ALS-like changes was considerably reduced.”

ALS is a devastating disease that hits people in the prime of life, causing increasing paralysis and often results in death within two to three years after diagnosis. At present, only two drugs are available that slow the disease modestly. This study offers the possibility that L-serine may slow the progression of the disease even more.

Potential Implications for L-Serine as a Treatment

Neurobiologist Dr. Deborah Mash of Nova Southeastern University, who was also an author on the study, said that the results “holds promise for identifying a cause of sporadic ALS, which accounts for 90 percent of all ALS cases.”

Dr. Elijah Stommel, a Professor of Neurology at Dartmouth Medical School, who was not associated with the study, said that these experimental results are encouraging. Stommel is conducting a Phase II trial of L-serine in 50 ALS patients. “We are attempting to replicate a previous positive trial of L-serine for ALS patients, but won’t know the results until the trial is finished,” he said.

L-serine is one of the twenty amino acids that make up human proteins. L-serine molecules in proteins are often the site where proteins are phosphorylated, or charged, so they can be properly folded. “Think of a charging port for an electric car,” explained Dr. Paul Alan Cox, Executive Director of the Brain Chemistry Labs in Jackson Hole, “If the cable can’t be connected there, the car can’t be charged.” Scientists at the Brain Chemistry Labs have also discovered that L-serine modulates the unfolded protein response which helps protect neurons from the damage produced by misfolded proteins.

“While these data provide valuable insights, we do not yet know if L-serine will improve outcomes for human patients with ALS,” cautioned internationally renowned ALS expert, Dr. Walter Bradley, who was also an author on the study. “We need to carefully continue FDA-approved clinical trials before we can recommend that L-serine be added to the neurologists’ toolbox for the treatment of ALS. However, this vervet BMAA model will be an important new tool in the quest for new drugs to treat ALS.”

Dr. Larry Brand, a prominent oceanographer unassociated with the study, said that there are even broader implications of the study for human health. “These vervets were exposed to the same cyanobacterial toxin that was found in the brains of beached dolphins with Alzheimer’s neuropathology,” he said. “This is one more indication that we need to carefully monitor the health effects of exposure to cyanobacterial blooms.”

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NEWS RELEASE 19-FEB-2020

Tart cherry juice concentrate found to help improve endurance exercise performance

WEBER SHANDWICK CHICAGO

 

Montmorency tart cherry juice has gained a reputation as a recovery drink among elite and recreational exercisers, with research suggesting benefits for reducing strength loss and improving muscle recovery after intensive exercise. Now, a new first-of-its-kind analysis published in the Journal of the American College of Nutrition found that tart cherries improved endurance exercise performance among study participants.

This new meta-analysis examined 10 previously published studies on tart cherries and exercise recovery. The sample sizes ranged from 8-27, and the average ages of study participants ranged from 18.6 to 34.6 years. Most of the participants were endurance-trained individuals, including cyclists, runners and triathletes. The 10 studies totaled 127 males and 20 females.

After pooling results from the 10 published studies, the meta-analysis concluded that tart cherry concentrate in juice or powdered form significantly improved endurance exercise performance when consumed for seven days to 1.5 hours before cycling, swimming or running.

“The recovery benefits of tart cherry concentrate are well researched, yet evidence on performance enhancement is scarce and results have been mixed,” said co-author Philip Chilibeck, PhD, professor in the College of Kinesiology at the University of Saskatchewan. “The results of this meta-analysis found that tart cherries did help improve performance, and we gained greater insight into the potential mechanism responsible for this benefit.”

Research Methodology

Researchers reviewed existing research related to tart cherries and aerobic endurance sport performance and identified 10 studies that fit the inclusion criteria. To qualify, studies were required to be randomized controlled trials conducted in a healthy adult population and use a placebo as a comparison for tart cherry supplementation (including tart cherry juice, tart cherry concentrate, tart cherry powder and tart cherry powder capsules).

Nine of the 10 studies involved longer-term tart cherry consumption (around two to seven days prior to exercise) and one involved same-day supplementation. Tart cherry dosages varied across studies and included 200 to 500 mg/day in capsule or powder form, 60 to 90 mL/day of tart cherry juice concentrate diluted with 100 to 510 mL water and 300 to 473mL/day of tart cherry juice. The total amount of anthocyanins consumed daily ranged from 66 to 2,760 mg.

Methods of measuring performance differed across studies, and included distance on a shuttle swimming test, time to exhaustion during high-intensity cycling, total work performed during cycling, cycling time trials (time it took to cover 10 km, 15 km and 20 km) and time to complete a full or half marathon. To account for these variations, researchers calculated standardized mean differences and 95% confidence intervals to assess performance changes.

Results

Pooled results across these 10 studies indicated a significant improvement in endurance performance with tart cherry concentrate, with two of the 10 studies reporting significant performance-enhancing effects on their own. While pooled results in the meta-analysis found significant benefits, eight of the 10 studies on recovery did not demonstrate a performance benefit when comparing tart cherry to placebo. This could be related to participant demographics and fitness levels, diet and exercise control, supplementation protocol and measurements of performance. Not all studies used well-trained athletes, and the meta-analysis found the lowest improvement when tart cherry juice was consumed by the lowest trained participants. No dose-response relationship was found between tart cherry concentrate and performance, and further studies are warranted to find an optimal dosing strategy.

Nearly all of the studies on cherries and recovery or performance have been conducted with Montmorency tart cherries, the most common variety of tart cherries grown in the U.S. These home-grown tart cherries are available year-round in dried, frozen, canned, juice and juice concentrate forms. Other varieties of tart cherries may be imported and not grown locally.

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Source: Gao R, Chilibeck PD. Effect of tart cherry concentrate on endurance exercise performance: a meta-analysis. Journal of the American College of Nutrition. 2020. [E-pub ahead of print].

Cherry Industry Administrative Board

The Cherry Industry Administrative Board (CIAB) is a not-for-profit organization funded by U.S. tart cherry growers and processors. CIAB had no role in the funding of this study. CIAB’s mission is to increase the demand for Montmorency tart cherries through promotion, market expansion and product development. To learn more about previous research studies on Montmorency tart cherries, visit ChooseCherries.com.

NEWS RELEASE 19-FEB-2020

People who eat a big breakfast may burn twice as many calories

Study finds eating more at breakfast instead of dinner could prevent obesity

THE ENDOCRINE SOCIETY

SHARE PRINT E-MAILWASHINGTON–Eating a big breakfast rather than a large dinner may prevent obesity and high blood sugar, according to new research published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Our body expends energy when we digest food for the absorption, digestion, transport and storage of nutrients. This process, known as diet-induced thermogenesis (DIT), is a measure of how well our metabolism is working, and can differ depending on mealtime.

“Our results show that a meal eaten for breakfast, regardless of the amount of calories it contains, creates twice as high diet-induced thermogenesis as the same meal consumed for dinner,” said the study’s corresponding author, Juliane Richter, M.Sc., Ph.D., of University of Lübeck in Germany. “This finding is significant for all people as it underlines the value of eating enough at breakfast.”

The researchers conducted a three-day laboratory study of 16 men who consumed a low-calorie breakfast and high-calorie dinner, and vice versa in a second round. They found identical calorie consumption led to 2.5 times higher DIT in the morning than in the evening after high-calorie and low-calorie meals. The food-induced increase of blood sugar and insulin concentrations was diminished after breakfast compared with dinner. The results also show eating a low-calorie breakfast increased appetite, specifically for sweets.

“We recommend that patients with obesity as well as healthy people eat a large breakfast rather than a large dinner to reduce body weight and prevent metabolic diseases,” Richter said.

NEWS RELEASE 24-FEB-2020

Recent research points the way toward a practical nutraceutical strategy for coping with RNA virus infections including influenza and coronavirus

Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses, as reported in Progress in Cardiovascular Diseases

ELSEVIER

Philadelphia, February 24, 2020 – In a compelling article in Progress in Cardiovascular Diseases, published by Elsevier, Mark McCarty of the Catalytic Longevity Foundation, San Diego, CA, USA, and James DiNicolantonio, PharmD, a cardiovascular research scientist at Saint Luke’s Mid America Heart Institute, Kansas City, MO, USA, propose that certain nutraceuticals may help provide relief to people infected with encapsulated RNA viruses such as influenza and coronavirus.

In the United States, influenza infects around 30 million people every year causing around 30,000 deaths. While there are medications approved for the treatment of influenza, they typically are costly, have side effects, and are not very effective. Additionally, vaccinations against influenza may only be effective in around 50 percent of those vaccinated. Thus, there is a need for safer and effective alternatives in those infected with influenza.

Over the past few months, a novel RNA coronavirus, now called COVID-19, has broken out in China and has spread to over two dozen countries and infected more than 76,000 people causing more than 2,000 deaths. This novel coronavirus is much more lethal than the typical flu, with a current mortality rate of about 2.92 percent. In other words, around 1 in 33 people who are infected with this novel coronavirus will die. Whereas the annual flu has a mortality rate of just 0.05 to 0.1 percent. This means that around 1 in 1,000 to 2,000 people infected with the annual flu will die. In other words, COVID-19 is around 30 to 60 times more lethal than the typical annual flu.

Both influenza and coronavirus cause an inflammatory storm in the lungs and it is this inflammatory storm that leads to acute respiratory distress, organ failure, and death. Certain nutraceuticals may help to reduce the inflammation in the lungs from RNA viruses and others may also help boost type 1 interferon response to these viruses, which is the body’s primary way to help create antiviral antibodies to fight off viral infections.

The authors draw attention to several randomized clinical studies in humans that have found that over the counter supplements such as n-acetylcysteine (NAC), which is used to treat acetaminophen poisoning and is also used as a mucus thinner to help reduce bronchitis exacerbations, and elderberry extracts, have evidence for shortening the duration of influenza by about two to four days and reducing the severity of the infection. The authors also note several nutraceuticals such as spirulina, beta-glucan, glucosamine, and NAC have either been found to reduce the severity of infection or to cut the rate of death in half in animals infected with influenza. Furthermore, one clinical study in humans testing spirulina noted significant reductions in viral load in those infected with HIV.

“Therefore, it is clear that certain nutraceuticals have antiviral effects in both human and animal studies,” commented Dr. DiNicolantonio. “Considering that there is no treatment for COVID-19 and treatments for influenza are limited, we welcome further studies to test these nutraceuticals as a strategy to help provide relief in those infected with encapsulated RNA viruses.”

Editor-in-Chief of Progress Cardiovascular Diseases Carl “Chip” Lavie, MD, Ochsner Clinical School-The University of Queensland School of Medicine, New Orleans, LA, USA, added, “Considering the recent interests directed at serious viral infections, especially coronavirus and influenza, this material should be of interest to specialists in cardiovascular diseases but also to a wide range of clinicians outside of our typical readership.”

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NEWS RELEASE 28-FEB-2020

When should you eat to manage your weight? Breakfast, not late-night snacks

PLOS

 

The balance between weight gain and weight gain loss is predominantly determined by what you eat, how much you eat, and by how much exercise you get. But another important factor is often neglected… Published February 27 in the open-access journal PLOS Biology, research conducted by Kevin Kelly, Owen McGuinness, Carl Johnson and colleagues of Vanderbilt University, USA shows that it’s not just how many calories you eat, but WHEN you eat them that will determine how well you burn those calories.

Your daily biological clock and sleep regulate how the food you eat is metabolized; thus the choice of burning fats or carbohydrates changes depending on the time of day or night. Your body’s circadian rhythm has programmed your body to burn fat when you sleep, so when you skip breakfast and then snack at night you delay burning the fat.

The researchers monitored the metabolism of mid-aged and older subjects in a whole-room respiratory chamber over two separate 56-hour sessions, using a “random crossover” experimental design. In each session, lunch and dinner were presented at the same times (12:30 and 17:45, respectively), but the timing of the third meal differed between the two halves of the study. Thus in one of the 56-hour bouts, the additional daily meal was presented as breakfast (8:00) whereas in the other session, a nutritionally equivalent meal was presented to the same subjects as a late-evening snack (22:00). The duration of the overnight fast was the same for both sessions.

Whereas the two sessions did not differ in the amount or type of food eaten or in the subjects’ activity levels, the daily timing of nutrient availability, coupled with clock/sleep control of metabolism, flipped a switch in the subjects’ fat/carbohydrate preference such that the late-evening snack session resulted in less fat burned when compared to the breakfast session. The timing of meals during the day/night cycle therefore affects the extent to which ingested food is used versus stored.

This study has important implications for eating habits, suggesting that a daily fast between the evening meal and breakfast will optimize weight management.

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NEWS RELEASE 27-FEB-2020

Extra olive virgin oil keeps healthy properties when used for cooking

Simulation of cooking conditions in a domestic kitchen

UNIVERSITY OF BARCELONA

 

Consuming extra virgin olive oil has proved to have protecting effects for the health, especially due to its antioxidant content. However, there are not many studies on whether it is the best oil to use when cooking. A study by the University of Barcelona stated this kind of oil keeps the levels of antioxidants -regarded as health- when used for cooking, a common technique in the Mediterranean cuisine. These results could be relevant for future recommendations or nutritional guidelines.

The study, published by the journal Antioxidants, counts on the participation of a team of researchers from the Faculty of Pharmacy and Food Sciences of the UB, the Physiopathology of Obesity and Nutrition Networking Biomedical Research Centre (CIBERobn) and the University of São Paulo.

Simulation of cooking conditions in a domestic kitchen

Extra virgin olive oil is the main source of fat of the Mediterranean diet and shows a unique composition of fatty acids with a higher content of antioxidants than other edible oils. Its benefits for the health are mainly linked to these compounds, named polyphenols. “The effects of cooking on these polyphenols of oil have always been studied in a laboratory or industrial situation, which is far from the reality of our homes”, says Rosa M. Lamuela, director of the Institute in Research on Nutrition and Food Safety (INSA-UB).

For this study, however, researchers simulated the cooking conditions of a domestic kitchen. The aim was to see how the homemade sauté affects the polyphenols of extra virgin olive oil. Researchers studied the effects of time -during a short and a long period of time- and temperature -at 120ºC and 170ºC- in the degradation of the antioxidants.

Results show that during the cooking process, the content of polyphenols decreased by 40% to 120ºC and by 75% at 170ºC, compared to the levels of antioxidants in raw oil. Moreover, the cooking time had an effect on individual phenols, such as hydroxytyrosol, but not on the total content of the phenol. As a whole, the levels of antioxidants keep fulfilling the parameters stated as healthy by the European Union: “Despite the decrease in concentration of polyphenols during the cooking process, this oil has a polyphenol level that reaches the declaration of health in accordance to the European regulation, which means it has properties that protect oxidation of LDL cholesterol particles”, notes Julián Lozano, first signer of the publication, which is also part of his doctoral thesis.

Olive oil in Mediterranean cuisine

The Mediterranean diet, known for a high use of phytochemicals from vegetables, fruits and legumes, has been correlated to improvements in cardiovascular and metabolic health. This link is based on the results of the PREDIMED study, a multicenter clinical study conducted from 2003 to 2011 with more than 7,000 people, in which Rosa M. Lamuela took part as well.

However, the effects on health in the Mediterranean diet have been hard to reproduce in non-Mediterranean populations. According to the researchers, this fact could occur due to, probably, differences in cooking practices. In this context, the results are added to previous studies by the research group which analyzed the effects of extra virgin olive oil in the sauté -with positive results. Thus, this strengthens the idea of the Mediterranean gastronomy being beneficial for our health, not only for its food but also for the ways of cooking it.

According to the authors, the current objective is to analyze the effects of cooking with extra virgin olive oil with other food elements, such as legumes, meat, etc. “Moreover, we should conduct random research studies in humans, in which we would compare the potential benefits we obtain when cooking with quality extra virgin olive oil compared to other oils”, concludes the researcher.

NEWS RELEASE 27-FEB-2020

Eat less, live longer

Salk scientists show how caloric restriction prevents negative effects of aging in cells

SALK INSTITUTE

LA JOLLA–(February 27, 2020) If you want to reduce levels of inflammation throughout your body, delay the onset of age-related diseases, and live longer–eat less food. That’s the conclusion of a new study by scientists from the US and China that provides the most detailed report to date of the cellular effects of a calorie-restricted diet in rats. While the benefits of caloric restriction have long been known, the new results show how this restriction can protect against aging in cellular pathways, as detailed in Cell on February 27, 2020.

“We already knew that calorie restriction increases life span, but now we’ve shown all the changes that occur at a single-cell level to cause that,” says Juan Carlos Izpisua Belmonte, a senior author of the new paper, professor in Salk’s Gene Expression Laboratory and holder of the Roger Guillemin Chair. “This gives us targets that we may eventually be able to act on with drugs to treat aging in humans.”

Aging is the highest risk factor for many human diseases, including cancer, dementia, diabetes and metabolic syndrome. Caloric restriction has been shown in animal models to be one of the most effective interventions against these age-related diseases. And although researchers know that individual cells undergo many changes as an organism ages, they have not known how caloric restriction might influence these changes.

In the new paper, Belmonte and his collaborators–including three alumni of his Salk lab who are now professors running their own research programs in China–compared rats who ate 30 percent fewer calories with rats on normal diets. The animals’ diets were controlled from age 18 months through 27 months. (In humans, this would be roughly equivalent to someone following a calorie-restricted diet from age 50 through 70.)

At both the start and the conclusion of the diet, Belmonte’s team isolated and analyzed a total of 168,703 cells from 40 cell types in the 56 rats. The cells came from fat tissues, liver, kidney, aorta, skin, bone marrow, brain and muscle. In each isolated cell, the researchers used single-cell genetic-sequencing technology to measure the activity levels of genes. They also looked at the overall composition of cell types within any given tissue. Then, they compared old and young mice on each diet.

Many of the changes that occurred as rats on the normal diet grew older didn’t occur in rats on a restricted diet; even in old age, many of the tissues and cells of animals on the diet closely resembled those of young rats. Overall, 57 percent of the age-related changes in cell composition seen in the tissues of rats on a normal diet were not present in the rats on the calorie restricted diet.

“This approach not only told us the effect of calorie restriction on these cell types, but also provided the most complete and detailed study of what happens at a single-cell level during aging,” says co-corresponding author Guang-Hui Liu, a professor at the Chinese Academy of Sciences.

Some of the cells and genes most affected by the diet related to immunity, inflammation and lipid metabolism. The number of immune cells in nearly every tissue studied dramatically increased as control rats aged but was not affected by age in rats with restricted calories. In brown adipose tissue–one type of fat tissue–a calorie-restricted diet reverted the expression levels of many anti-inflammatory genes to those seen in young animals.

“The primary discovery in the current study is that the increase in the inflammatory response during aging could be systematically repressed by caloric restriction” says co-corresponding author Jing Qu, also a professor at the Chinese Academy of Sciences.

When the researchers homed in on transcription factors–essentially master switches that can broadly alter the activity of many other genes–that were altered by caloric restriction, one stood out. Levels of the transcription factor Ybx1 were altered by the diet in 23 different cell types. The scientists believe Ybx1 may be an age-related transcription factor and are planning more research into its effects.

“People say that ‘you are what you eat,’ and we’re finding that to be true in lots of ways,” says Concepcion Rodriguez Esteban, another of the paper’s authors and a staff researcher at Salk. “The state of your cells as you age clearly depends on your interactions with your environment, which includes what and how much you eat.”

The team is now trying to utilize this information in an effort to discover aging drug targets and implement strategies towards increasing life and health span.

NEWS RELEASE 26-FEB-2020

Antioxidant precursor molecule could improve brain function in patients with MS

The naturally occurring molecule N-acetylcysteine (NAC) shows benefit in a clinical trial for multiple sclerosis

THOMAS JEFFERSON UNIVERSITY

(PHILADELPHIA) – N-acetylcysteine (NAC) is a naturally occurring molecule that replenishes antioxidants and shows improved brain metabolism and self-reported improvements in cognitive function in patients with multiple sclerosis, according to a study published in the journal, Frontiers in Neurology.

The study found improvements in brain metabolism, particularly in areas that support cognition such as the frontal and temporal lobes in patients with multiple sclerosis. In addition, patients reported qualitative improvements in their cognitive and attention focusing abilities. The study was performed by the Department of Integrative Medicine and Nutritional Sciences, as well as the Departments of Neurology and Radiology, at Thomas Jefferson University.

Current treatments for multiple sclerosis are generally limited to trying to slow the progression of the disease by preventing new brain lesions from occurring. However, these approaches do not help the neurons that have already been affected by the disease process. While the primary event of multiple sclerosis results from an immunological process that targets the white matter, the actual damage to neurons may be due in large part from oxidative stress caused by the immune reaction. NAC is an oral supplement, and also comes in an intravenous form that is used to protect the liver in acetaminophen overdose. Several initial studies have shown that NAC administration increases glutathione levels in the brain. Because glutathione is an antioxidant, researchers have proposed that it could reduce the oxidative stress from the immune reaction, though it’s unclear whether it would improve the function of neurons. The current study tested this by tracking cerebral glucose metabolism on positron emission tomography (PET) brain, as a proxy for normal neuronal function.

“This study is an important step in understanding how NAC might work as a potentially new avenue for managing multiple sclerosis patients. The NAC appears to enable neurons to recover some of their metabolic function,” says senior author on the paper Daniel Monti, MD, Chairman of the Department of Integrative Medicine and Nutritional Sciences and Director of the Marcus Institute of Integrative Health at Thomas Jefferson University.

Researchers evaluated 24 patients with multiple sclerosis who continued their current treatment and were placed into two groups – the first group received a combination of oral and intravenous (IV) NAC for two months (in addition to their current treatment program); and the second group, the control patients, received only their standard-of-care treatment for multiple sclerosis for two months. Patients were not blinded. Those patients in the active group received 50mg/kg NAC intravenously once per week and 500mg NAC orally 2x per day on the non IV days.

All patients underwent brain scanning using FDG PET imaging which measures the amount of glucose metabolism in the neurons throughout the brain. This test was used to determine the level of neuronal recovery. Patients were evaluated initially and after two months of either receiving the NAC or standard of care therapy. Patients were also evaluated clinically using several different measures of brain function and quality of life.

Compared to controls, the patients receiving NAC had significant improvements in brain metabolism in the caudate, inferior frontal gyrus, lateral temporal gyrus, and middle temporal gyrus as measured by FDG PET imaging. These areas are particularly important in supporting cognition and attention, which were both perceived by patients to be improved via self-reported questionnaires of overall health and well-being.

“This is an exciting study that suggests a natural molecule such as NAC may help improve brain metabolism and symptoms in patients with multiple sclerosis,” says corresponding author and neuro-imaging expert Andrew Newberg, MD, Professor and Director of Research at the Department of Integrative Medicine and Nutritional Sciences. The investigators hope that this research will open up new avenues of treatment for multiple sclerosis patients.

Manufacturers

NEWS RELEASE 3-MAR-2020

Can’t sleep? Prebiotics could help

Dietary compounds found to influence gut metabolites, buffering stress

UNIVERSITY OF COLORADO AT BOULDER

Think dietary fiber is just for digestive health? Think again.

Specific fibers known as prebiotics can improve sleep and boost stress resilience by influencing gut bacteria and the potent biologically active molecules, or metabolites, they produce, new University of Colorado Boulder research shows.

The research could ultimately lead to new approaches to treating sleep problems, which affect 70 million Americans.

“The biggest takeaway here is that this type of fiber is not just there to bulk up the stool and pass through the digestive system,” said Robert Thompson, a postdoctoral researcher in the Department of Integrative Physiology and lead author of the study, published today in the journal Scientific Reports. “It is feeding the bugs that live in our gut and creating a symbiotic relationship with us that has powerful effects on our brain and behavior.”

Food for our bugs

Most people are familiar with probiotics, friendly bacteria present in fermented foods like yogurt and sauerkraut. More recently, scientists have taken an interest in prebiotics – dietary compounds that humans cannot digest but serve as nourishment for our microbiome, or the trillions of bacteria residing within us. While not all fibers are prebiotics, many fibrous foods like leeks, artichokes, onions and certain whole grains are rich in them.

For the study, the researchers started adolescent male rats on either standard chow or chow infused with prebiotics and tracked an array of physiological measures before and after the rats were stressed.

As reported in the researchers’ previous study, those on the prebiotic diet spent more time in restorative non-rapid-eye-movement (NREM) sleep. After stress, they also spent more time in rapid-eye-movement (REM) sleep, which is believed to be critical for recovery from stress.

While rats eating standard chow saw an unhealthy flattening of the body’s natural temperature fluctuations and a drop in healthy diversity of their gut microbiome after stress, those fed prebiotics were buffered from these effects.

The new study sheds light on how prebiotics can help bust stress.

“We know that this combination of dietary fibers helps promote stress robustness and good sleep and protects the gut microbiome from disruption. With this new study, we wanted to try to identify the signal,” said senior author and Integrative Physiology Professor Monika Fleshner, director of the Stress Physiology Laboratory.

Using a technology called mass spectrometry to analyze the rats’ fecal samples, the researchers measured metabolites, or bioactive small molecules produced by bacteria as food is broken down.

They found rats on the prebiotic diet had a substantially different “metabolome”, or make-up of metabolites. Theirs was higher in dozens of them, including fatty acids, sugars and steroids which may, via gut-brain signaling pathways, influence behavior. The rats’ metabolome also looked different after stress.

For instance, the rats on the standard chow diet saw dramatic spikes in allopregnanolone precursor and Ketone Steroid, potentially sleep-disrupting metabolites, while those on the prebiotic diet saw no such spike.

“Our results reveal novel signals that come from gut microbes that may modulate stress physiology and sleep,” said Fleshner.

In search of a better sleeping pill

While prebiotic dietary fiber is certainly healthy, it’s uncertain whether just loading up on foods rich in it can promote sleep. The rats were fed very high doses of four specific prebiotics, including: galactooligosaccharides, which are present in lentils and cabbage; polydextrose (PDX) an FDA-approved food additive often used as a sweetener; lactoferrin, found in breast milk; and milk fat globular protein, abundant in dairy products.

“You’d probably have to eat a whole lot of lentils and cabbage to see any effect,” said Thompson.

Prebiotic supplements already abound on natural food store shelves. But Fleshner said it’s too soon to say whether a supplement or drug containing such compounds would be safe and effective for everyone. Depending on what their microbial make-up is, different people might respond differently.

“These are powerful molecules with real neuroactive effects and people need to exercise some caution,” she said.

Human studies are already in the works at CU Boulder.

Ultimately, Fleshner believes what they are learning in her lab could lead to a new class of options for people who can’t sleep but don’t like taking narcotics.

“Armed with this information, we might be able to develop a targeted therapeutic that boosts the molecules that buffer against stress and tamps down the ones that seem to disrupt sleep,” she said. “It’s exciting to think about.”

NEWS RELEASE 3-MAR-2020

Alzheimer’s: Can an amino acid help to restore memories?

CNRS

Scientists at the Laboratoire des Maladies Neurodégénératives (CNRS/CEA/Université Paris-Saclay) and the Neurocentre Magendie (INSERM/Université de Bordeaux) have just shown that a metabolic pathway plays a determining role in Alzheimer’s disease’s memory problems. This work, published on 3 March 2020 in Cell Metabolism, also shows that supplying a specific amino acid as a nutritional supplement in a mouse model of Alzheimer’s restores spatial memory affected early. This is a promising path for reducing memory loss related to that disease.

The brain uses a large part of the energy available to our body. To work properly, neurons and the surrounding cells, particularly astrocytes, must cooperate. The early phase of Alzheimer’s disease is characterized by a reduction in this energy metabolism, but until now we did not know whether this deficit contributed directly to the cognitive symptoms of Alzheimer’s disease.

A collaborative study has shown in a mouse model of Alzheimer’s disease that a decrease in the use of glucose by astrocytes reduces L-serine production. This amino acid is mainly produced by these brain cells and its biosynthesis path is altered in patients. L-serine is the precursor of D-serine, known to stimulate NMDA receptors, essential for brain function and to the establishment of memory. So by producing less L-serine, astrocytes cause reduced activity in these receptors, which alters neuronal plasticity and the associated memorization capacities. Scientists have also demonstrated that memorization functions in mice were restored by supplying nutritional L-serine.

With the identification of the role of L-serine in memory disorders and the experimental efficacy of nutritional supplementation, new strategies appear that may complement medical treatment, to combat early symptoms of Alzheimer’s disease and other diseases that display metabolic deficits, like Parkinson’s and Huntington’s. Since L-serine is available as a nutritional supplement, this compound should be rigorously tested in humans, through controlled clinical trials.

NEWS RELEASE 6-MAR-2020

Low blood pressure linked to high mortality in older adults

International blood pressure guidelines may require review, according to new research that found a link between low blood pressure and higher mortality rates

UNIVERSITY OF EXETER

found a link between low blood pressure and higher mortality rates.

A largescale study led by the University of Exeter, published in Age and Ageing and funded by NIHR, analysed 415,980 electronic medical records of older adults in England.

The research was conducted after some countries have changed blood pressure guidelines to encourage clinicians to take measures to reduce blood pressure in a bid to improve health outcomes. UK blood pressure guidelines are within safe parameters for all. However, previous research has not considered the impact on frail older adults, who are often omitted from trials.

The team found that people aged 75 or over with low blood pressure (below 130 / 80) had increased mortality rates in the follow-up, compared to those with normal blood pressure. This was especially pronounced in ‘frail’ individuals, who had 62 per cent increased risk of death during the ten year follow-up.

Although high blood pressure increased risk of cardiovascular incidents, such as heart attacks, it was not linked to higher mortality in frail adults over 75. Older people aged 85 and over who had raised blood pressure actually had reduced mortality rates, compared to those with lower blood pressure, regardless of whether they were frail or not.

Jane Masoli, a geriatrician and NIHR Doctoral Research Fellow, who led the study as part of her PhD at the University of Exeter, said: “Internationally, guidelines are moving towards tight blood pressure targets, but our findings indicate that this may not be appropriate in frail older adults. We need more research to ascertain whether aggressive blood pressure control is safe in older adults, and then for which patient groups there may be benefit, so we can move towards more personalised blood pressure management in older adults.”

She added: “We know that treating blood pressure helps to prevent strokes and heart attacks and we would

NEWS RELEASE 6-MAR-2020

Gut bacteria can penetrate tumors and aid cancer therapy, study suggests

ROCKEFELLER UNIVERSITY PRESS

 

Researchers at the University of Texas Southwestern Medical Center and University of Chicago have discovered that bacteria that usually live in the gut can accumulate in tumors and improve the effectiveness of immunotherapy in mice. The study, which will be published March 6 in the Journal of Experimental Medicine (JEM), suggests that treating cancer patients with Bifidobacteria might boost their response to CD47 immunotherapy, a wide-ranging anti-cancer treatment that is currently being evaluated in several clinical trials.

CD47 is a protein expressed on the surface of many cancer cells, and inhibiting this protein can allow the patient’s immune system to attack and destroy the tumor. Antibodies targeting CD47 are currently being tested as treatments for a wide variety of cancers in multiple clinical trials. But studies with laboratory mice have so far yielded mixed results: some mice seem to respond to anti-CD47 treatment, while others do not.

A team of researchers led by Yang-Xin Fu at the University of Texas Southwestern Medical Center and Ralph R. Weichselbaum, co-director of The Ludwig Center for Metastasis Research at the University of Chicago, found that the response to treatment depends on the type of bacteria living in the animals’ guts.

Tumor-bearing mice that normally respond to anti-CD47 treatment failed to respond if their gut bacteria were killed off by a cocktail of antibiotics. In contrast, anti-CD47 treatment became effective in mice that are usually non-responsive when these animals were supplemented with Bifidobacteria, a type of bacteria that is often found in the gastrointestinal tract of healthy mice and humans. Bifidobacteria have previously been shown to benefit patients with ulcerative colitis.

Surprisingly, however, the researchers found that Bifidobacteria do not just accumulate in the gut; they also migrate into tumors, where they appear to activate an immune signaling pathway called the stimulation of interferon genes (STING) pathway. This results in the production of further immune signaling molecules and the activation of immune cells. When combined with anti-CD47 treatment, these activated immune cells can attack and destroy the surrounding tumor.

“Our study demonstrates that a specific member of the gut microbial population enhances the anti-tumor efficacy of anti-CD47 by colonizing the tumor,” Fu says. “Administration of specific bacterial species or their engineered progenies may be a novel and effective strategy to modulate various anti-tumor immunotherapies.”

“Our results open a new avenue for clinical investigations into the effects of bacteria within tumors and may help explain why some cancer patients fail to respond to immunotherapy,” says Weichselbaum.

NEWS RELEASE 5-MAR-2020

Curcumin is the spice of life when delivered via tiny nanoparticles

Treatment for Alzheimer’s and genital herpes

UNIVERSITY OF SOUTH AUSTRALIA

For years, curry lovers have sworn by the anti-inflammatory properties of turmeric, but its active compound, curcumin, has long frustrated scientists hoping to validate these claims with clinical studies.

The failure of the body to easily absorb curcumin has been a thorn in the side of medical researchers seeking scientific proof that curcumin can successfully treat cancer, heart disease, Alzheimer’s and many other chronic health conditions.

Now, researchers from the University of South Australia (UniSA), McMaster University in Canada and Texas A&M University have shown that curcumin can be delivered effectively into human cells via tiny nanoparticles.

Sanjay Garg, a professor of pharmaceutical science at UniSA, and his colleague Dr Ankit Parikh are part of an international team that has developed a nano formulation which changes curcumin’s behaviour to increase its oral bioavailability by 117 per cent.

The researchers have shown in animal experiments that nanoparticles containing curcumin not only prevents cognitive deterioration but also reverses the damage. This finding paves the way for clinical development trials for Alzheimer’s.

Co-author Professor Xin-Fu Zhou, a UniSA neuroscientist, says the new formulation offers a potential solution for Alzheimer’s disease.

“Curcumin is a compound that suppresses oxidative stress and inflammation, both key pathological factors for Alzheimer’s, and it also helps remove amyloid plaques, small fragments of protein that clump together in the brains of Alzheimer disease patients,” Prof Zhou says.

The same delivery method is now being tested to show that curcumin can also prevent the spread of genital herpes.

“To treat genital herpes (HSV-2) you need a form of curcumin that is better absorbed, which is why it needs to be encapsulated in a nano formulation,” Prof Garg says.

“Curcumin can stop the genital herpes virus, it helps in reducing the inflammation and makes it less susceptible to HIV and other STIs,” Prof Garg says.

Women are biologically more vulnerable to genital herpes as bacterial and viral infections in the female genital tract (FGT) impair the mucosal barrier. Curcumin, however, can minimize genital inflammation and control against HSV-2 infection, which would assist in the prevention of HIV infection in the FGT.

NEWS RELEASE 5-MAR-2020

Consuming more olive oil associated with less heart disease in Americans

American Heart Association EPI | LIFESTYLE 2020 Scientific Sessions – Abstract P509

AMERICAN HEART ASSOCIATION

PHOENIX, March 5, 2020 — Consuming more olive oil was associated with less risk of heart attack among Americans, especially when it replaced mayonnaise, margarine or butter, according to preliminary research presented today at the American Heart Association’s Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2020. The EPI Scientific Sessions is a premier global exchange of the latest advances in population based cardiovascular science for researchers and clinicians.

After accounting for diet and lifestyle factors, researchers found that those who ate more than half a tablespoon per day of olive oil had a 15% lower risk of having any kind of cardiovascular disease and a 21% lower risk of coronary heart disease. However, higher consumption of olive oil did not show an impact on stroke risk.

The researchers also found that replacing one teaspoon of butter, margarine, mayonnaise or dairy fat with the same amount of olive oil lowered the risk of any cardiovascular disease by 5% and lowered the risk of coronary heart disease by 7%. However, when the study began in 1990, many margarines contained substantial amounts of trans-fatty acids, so the results may not apply to vegetable margarines currently available.

“Previous studies have linked high consumption of olive oil with better cardiovascular health, particularly in Mediterranean countries where olive oil intake is much higher than in the United States,” said Marta Guasch-Ferre, Ph.D., lead author of the study and a research scientist in the department of nutrition at Harvard T.H. Chan School of Public Health in Boston.

“Our aim was to investigate whether higher olive oil consumption was beneficial to heart health in the U.S. population,” Guasch-Ferre said.

This study took place between 1990 and 2014 and included 63,867 women from the Nurses’ Health Study and 35,512 men from the Health Professionals Follow-up Study. All participants were free of cancer, heart disease and other chronic diseases at the start of the study. Every four years for about three decades, study participants answered questionnaires about their diet and lifestyle.

Researchers also used statistical models to compare the cardiovascular health benefits of olive oil with other plant oils combined, such as corn, canola, safflower and soybean. “One interesting thing our study shows is that although olive oil was better than most animal fats and margarine, it was not superior to vegetable oils in this study population,” Guasch-Ferre said. “This means that replacing any type of animal fat with vegetable oils, including olive oil but also others, could be a good strategy to improve cardiovascular health.”

The study findings were observational, which means they don’t prove cause and effect. However, small intervention studies have found benefits of replacing animal fats with olive oil on blood lipids. “Future research is needed to investigate the mechanisms behind this association as well as the effects of other vegetable oils on heart health,” said Guasch-Ferre. The study was also limited by the fact that the data was self-reported by the participants. However, repeated measures of diet used in the study can help to improve accuracy of dietary measurements.

“Using vegetable oils in cooking and in salads makes good sense,” said Penny Kris-Etherton, Ph.D., R.D.N., the chair of the American Heart Association’s Lifestyle and Cardiometabolic Health Council and distinguished professor of nutrition at The Pennsylvania State University, College of Health and Human Development in University Park. “Research has overwhelmingly found that diets that are rich in plant-based foods, including healthier vegetable oils such as olive, safflower, corn and many others, can significantly benefit heart health. Butter and tropical oils (palm oil and coconut oil) are both high in saturated fat, which raises LDL cholesterol (“bad cholesterol”) in many people. Margarine made with vegetable oil is also a source of healthy fats.”

NEWS RELEASE 4-MAR-2020

Study shows low carb diet may prevent, reverse age-related effects within the brain

STONY BROOK UNIVERSITY

STONY BROOK, NY, March 4, 2020 – A study using neuroimaging led by Stony Brook University professor and lead author Lilianne R. Mujica-Parodi, PhD, and published in PNAS, reveals that neurobiological changes associated with aging can be seen at a much younger age than would be expected, in the late 40s. However, the study also suggests that this process may be prevented or reversed based on dietary changes that involve minimizing the consumption of simple carbohydrates.

To better understand how diet influences brain aging, the research team focused on the presymptomatic period during which prevention may be most effective. In the article titled “Diet modulates brain network stability, a biomarker for brain aging, in young adults,” they showed, using large-scale life span neuroimaging datasets, that functional communication between brain regions destabilizes with age, typically in the late 40’s, and that destabilization correlates with poorer cognition and accelerates with insulin resistance. Targeted experiments then showed this biomarker for brain aging to be reliably modulated with consumption of different fuel sources: glucose decreases, and ketones increase, the stability of brain networks. This effect was replicated across both changes to total diet as well as after drinking a fuel-specific calorie-matched supplement.

“What we found with these experiments involves both bad and good news,” said Mujica-Parodi, a Professor in the Department of Biomedical Engineering with joint appointments in the College of Engineering & Applied Sciences and Renaissance School of Medicine at Stony Brook University, and a faculty member in the Laufer Center for Physical and Quantitative Biology. “The bad news is that we see the first signs of brain aging much earlier than was previously thought. However, the good news is that we may be able to prevent or reverse these effects with diet, mitigating the impact of encroaching hypometabolism by exchanging glucose for ketones as fuel for neurons.”

What the researchers discovered, using neuroimaging of the brain, is that quite early on there is breakdown of communication between brain regions (“network stability”).

“We think that, as people get older, their brains start to lose the ability to metabolize glucose efficiently, causing neurons to slowly starve, and brain networks to destabilize,” said Mujica-Parodi. “Thus, we tested whether giving the brain a more efficient fuel source, in the form of ketones, either by following a low-carb diet or drinking ketone supplements, could provide the brain with greater energy. Even in younger individuals, this added energy further stabilized brain networks.”

To conduct their experiments, brain network stability was established as a biomarker for aging by using two large-scale brain neuroimaging (fMRI) datasets totaling nearly 1,000 individuals, ages 18 to 88. Destabilization of brain networks was associated with impaired cognition and was accelerated with Type 2 diabetes, an illness that blocks neurons’ ability to effectively metabolize glucose. To identify the mechanism as being specific to energy availability, the researchers then held age constant and scanned an additional 42 adults under the age of 50 years with fMRI. This allowed them to observe directly the impact of glucose and ketones on each individual’s brain.

The brain’s response to diet was tested in two ways. The first was holistic, comparing brain network stability after participants had spent one week on a standard (unrestricted) vs. low carb (for example: meat or fish with salad, but no sugar, grains, rice, starchy vegetables) diet. In a standard diet, the primary fuel metabolized is glucose, whereas in a low-carb diet, the primary fuel metabolized is ketones. However, there might have been other differences between diets driving the observed effects. Therefore, to isolate glucose vs. ketones as the crucial difference between the diets, an independent set of participants was scanned before and after drinking a small dose of glucose on one day, and ketones on the other, where the two fuels were individually weight-dosed and calorically matched. The results replicated, showing that the differences between the diets could be attributed to the type of fuel they provide to the brain.

Additional findings from the study included the following: Effects of brain aging emerged at age 47, with most rapid degeneration occurring at age 60. Even in younger adults, under age 50, dietary ketosis (whether achieved after one week of dietary change or 30 minutes after drinking ketones) increased overall brain activity and stabilized functional networks. This is thought to be due to the fact that ketones provide greater energy to cells than glucose, even when the fuels are calorically matched. This benefit has previously been shown for the heart, but the current set of experiments provides the first evidence for equivalent effects in the brain.

“This effect matters because brain aging, and especially dementia, are associated with “hypometabolism,” in which neurons gradually lose the ability to effectively use glucose as fuel. Therefore, if we can increase the amount of energy available to the brain by using a different fuel, the hope is that we can restore the brain to more youthful functioning. In collaboration with Dr. Eva Ratai at Massachusetts General Hospital, we’re currently addressing this question, by now extending our studies to older populations,” said Mujica-Parodi.

“Additional research with collaborators at Children’s National, under the direction of Dr. Nathan Smith, focuses on discovering the precise mechanisms by which fuel impacts signaling between neurons. Finally, in collaboration with Dr. Ken Dill and Dr. Steven Skiena, at Stony Brook, we’re working on building a comprehensive computational model that can incorporate our understanding of the biology, from individual neurons to whole brains to cognition, as it develops.”

The research is currently funded under a new $2.5 million National Science Foundation BRAIN Initiative “Frontiers” grants (numbers (NSFECCS1533257 and NSFNCS-FR 1926781) awarded to Stony Brook, as well as by the W. M. Keck Foundation, which originally funded the team in 2017 with a $1 million seed grant designed to jump-start “pioneering discoveries in science, engineering, and medical research.”

NEWS RELEASE 4-MAR-2020

Fish oil supplements linked to lower risk of heart disease and death

Further studies should explore what dose is needed to achieve a clinically meaningful effect

Regular use of fish oil supplements may be linked to a lower risk of death and cardiovascular disease (CVD) events, such as heart attack and stroke, suggests an analysis of data from the UK Biobank study, published in The BMJ today.

Further studies should explore what dose is needed to achieve a clinically meaningful effect, say the researchers.

Fish oil is a popular dietary supplement in the UK and other developed countries. Some evidence suggests that omega-3 fatty acids in fish oil may help prevent cardiovascular disease and reduce mortality, but conclusive evidence is still lacking.

To explore these potential associations further, a team of researchers based in China and the US drew on data from the UK Biobank – a large population based study of more than half a million British men and women.

Their analysis included 427,678 men and women aged between 40 and 69 years old, without CVD or cancer, who were enrolled in the study from 2006 to 2010 and completed a questionnaire on supplement use, including fish oil.

Death certificates and hospital records were used to monitor deaths from any cause (“all-cause mortality”), CVD deaths, and CVD events, such as heart attack and stroke, through to 2018.

Almost a third (31%) of participants reported taking regular fish oil supplements at the start of the study.

The researchers found that fish oil supplements were associated with a 13% lower risk of all-cause mortality, a 16% lower risk of CVD mortality, and a 7% lower risk of CVD events (388 fewer all-cause deaths, 124 fewer CVD deaths, and 295 fewer CVD events per 100,000 people in a median follow-up of 9 years).

The association between fish oil use and CVD events appeared to be stronger among those with high blood pressure.

These favourable associations remained after taking account of traditional risk factors, such as age, sex, lifestyle habits, diet, medication and other supplement use.

Results were also unchanged after further analyses, suggesting that the findings withstand scrutiny.

Several mechanisms could explain these results, say the researchers. For example, omega-3 fatty acid supplements have shown beneficial effects on blood pressure, cholesterol levels, and heart rate, all of which would exert a protective effect against the development of CVD events.

Despite the large sample size, this is an observational study, so can’t establish cause, and the researchers point to some limitations, such as lack of information on dose, duration, and side effects of fish oil use.

But they conclude that habitual fish oil use “is associated with a lower risk of all-cause and CVD mortality and a marginal benefit against CVD events among the general population.

Future studies are needed to address the extent to which the dose of fish oil supplements influences the ability to achieve a clinically meaningful effect,” they add.

NEWS RELEASE 17-MAR-2020

Life expectancy crisis in the USA: The opioid crisis is not the decisive factor

Cardiovascular diseases — rather than drug deaths due to the opioid crisis — have the greatest impact on stagnating life expectancy in the USA

MAX-PLANCK-GESELLSCHAFT

Life expectancy in the USA is no longer rising. This stagnation has long been largely attributed to increasing numbers of drug deaths due to the opioid crisis. But Mikko Myrskylä and colleagues have now shown that deaths due to cardiovascular diseases are in fact having a much larger impact on life expectancy.

Over each decade of the past century, life expectancy in the USA rose by two years. This is no longer the case. Since 2010, life expectancy has not improved. Until now, this fact has mainly been attributed to the rising number of drug deaths due to the opioid crisis.

But Mikko Myrskylä, Director of the Max Planck Institute for Demographic Research in Rostock, together with Neil Mehta and Leah Abrams from University of Michigan have shown a stall in declining cardiovascular deaths is a more likely explanation for the end of stagnation of life expectancy. They have published their findings in the scientific journal PNAS.

Drug-related deaths have little influence on life expectancy

The remaining life expectancy of 25-year-old Americans would have risen by 1.1 years between 2010 and 2017 if deaths from cardiovascular diseases had declined as much over that period as they did between 2000 and 2009.

By contrast, the rising number of drug-related deaths had a much smaller influence on life expectancy. “If the number of drug-related deaths had remained constant after 2010, male life expectancy would have risen just 0.4 years, or by around five months,” Mikko Myrskylä explained. Thus, over the long run, reducing the number of drug-related deaths will not be sufficient to ensure that life expectancy in the USA resumes its upward trajectory.

NEWS RELEASE 25-MAR-2020

Analysis predicts purified fish oil could prevent thousands of cardiovascular events

Abstract to be presented at American College of Cardiology/World Congress of Cardiology

UNIVERSITY OF CALIFORNIA – IRVINE

Irvine, CA – March 25, 2020 – Researchers from the University of California, Irvine have conducted a statistical analysis that predicts more than 70,000 heart attacks, strokes and other adverse cardiovascular events could be prevented each year in the U.S. through the use of a highly purified fish oil therapy.

Led by Nathan D. Wong, PhD, professor and director of the Heart Disease Prevention Program in the Division of Cardiology at the UCI School of Medicine, the abstract of the statistical analysis was accepted by the American College of Cardiology and is slated to be presented at the upcoming ACC.20/World Congress of Cardiology virtual conference taking place March 28-30. The analysis utilizes data from the Centers for Disease Control and Prevention’s National Health and Nutrition Examination Survey (NHANES), and inclusion criteria from a multinational clinical trial led by investigators from Harvard University called REDUCE-IT, which was published in the New England Journal of Medicine in January of 2019.

The REDUCE-IT trial showed patients with known cardiovascular disease or diabetes and multiple risk factors who have elevated triglyceride levels and are at increased risk for ischemic events benefitted substantially from icosapent ethyl, a highly purified fish oil therapy, which lowered cardiovascular events, including heart attacks and strokes, by 25 percent. Positive results were not found in other trials, possibly due to mixtures with other omega-3 fatty acids such as DHA, or inadequate dosages according to Wong.

“Our analysis extends the findings of the REDUCE-IT trial by estimating its potential impact on the U.S. population,” said Wong. “By using inclusion criteria and cardiovascular disease event rates from the REDUCE-IT trial and applying it to data on US adults from NHANES, we were able to estimate the beneficial impact icosapent ethyl could have on preventing initial and total cardiovascular events in eligible U.S. adults with cardiovascular disease or diabetes and multiple risk factors.”

Wong’s analysis is the first to project the findings of REDUCE-IT to the overall U.S. population.

“When you consider that for every 21 patients treated with icosapent ethyl you can spare a cardiovascular event, you begin to see the implications of our results,” said Wong.

Icosapent ethyl is a purified stable eicosapentaenoic acid (EPA) which was recently approved by the Federal Drug Administration (FDA) in conjunction with maximally tolerated statin therapy to reduce the risk of cardiovascular events in certain adults with elevated triglyceride levels. The only drug of its kind to show such an effect, icosapent ethyl, is currently marketed under the name Vascepa® by Amarin Pharma. The EPA therapy has also gained the support of several major societies, which have incorporated it in various guidelines, scientific statements and advisories, including the American Diabetes Association, American Heart Association, National Lipid Association, and the European Society of Cardiology/European Atherosclerosis Society.

NEWS RELEASE 25-MAR-2020

Too much salt weakens the immune system

Study by the University Hospital of Bonn shows: A diet rich in salt weakens the antibacterial immune defense

UNIVERSITY OF BONN

A high-salt diet is not only bad for one’s blood pressure, but also for the immune system. This is the conclusion of a current study under the leadership of the University Hospital Bonn. Mice fed a high-salt diet were found to suffer from much more severe bacterial infections. Human volunteers who consumed an additional six grams of salt per day also showed pronounced immune deficiencies. This amount corresponds to the salt content of two fast food meals. The results are published in the journal Science Translational Medicine.

Five grams a day, no more: This is the maximum amount of salt that adults should consume according to the recommendations of the World Health Organization (WHO). It corresponds approximately to one level teaspoon. In reality, however, many Germans exceed this limit considerably: Figures from the Robert Koch Institute suggest that on average men consume ten, women more than eight grams a day.

This means that we reach for the salt shaker much more than is good for us. After all, sodium chloride, which is its chemical name, raises blood pressure and thereby increases the risk of heart attack or stroke. But not only that: “We have now been able to prove for the first time that excessive salt intake also significantly weakens an important arm of the immune system,” explains Prof. Dr. Christian Kurts from the Institute of Experimental Immunology at the University of Bonn.

This finding is unexpected, as some studies point in the opposite direction. For example, infections with certain skin parasites in laboratory animals heal significantly faster if these consume a high-salt diet: The macrophages, which are immune cells that attack, eat and digest parasites, are particularly active in the presence of salt. Several physicians concluded from this observation that sodium chloride has a generally immune-enhancing effect.

The skin serves as a salt reservoir

“Our results show that this generalization is not accurate,” emphasizes Katarzyna Jobin, lead author of the study, who has since transferred to the University of Würzburg. There are two reasons for this: Firstly, the body keeps the salt concentration in the blood and in the various organs largely constant. Otherwise important biological processes would be impaired. The only major exception is the skin: It functions as a salt reservoir of the body. This is why the additional intake of sodium chloride works so well for some skin diseases.

However, other parts of the body are not exposed to the additional salt consumed with food. Instead, it is filtered out by the kidneys and excreted in the urine. And this is where the second mechanism comes into play: The kidneys have a sodium chloride sensor that activates the salt excretion function. As an undesirable side effect, however, this sensor also causes so-called glucocorticoids to accumulate in the body. And these in turn inhibit the function of granulocytes, the most common type of immune cell in the blood.

Granulocytes, like macrophages, are scavenger cells. However, they do not attack parasites, but mainly bacteria. If they do not do this to a sufficient degree, infections proceed much more severely. “We were able to show this in mice with a listeria infection,” explains Dr. Jobin. “We had previously put some of them on a high-salt diet. In the spleen and liver of these animals we counted 100 to 1,000 times the number of disease-causing pathogens.” Listeria are bacteria that are found for instance in contaminated food and can cause fever, vomiting and sepsis. Urinary tract infections also healed much more slowly in laboratory mice fed a high-salt diet.

Sodium chloride also appears to have a negative effect on the human immune system. “We examined volunteers who consumed six grams of salt in addition to their daily intake,” says Prof. Kurts. “This is roughly the amount contained in two fast food meals, i.e. two burgers and two portions of French fries.” After one week, the scientists took blood from their subjects and examined the granulocytes. The immune cells coped much worse with bacteria after the test subjects had started to eat a high-salt diet.

In human volunteers, the excessive salt intake also resulted in increased glucocorticoid levels. That this inhibits the immune system is not surprising: The best-known glucocorticoid cortisone is traditionally used to suppress inflammation. “Only through investigations in an entire organism were we able to uncover the complex control circuits that lead from salt intake to this immunodeficiency,” stresses Kurts. “Our work therefore also illustrates the limitations of experiments purely with cell cultures.”

NEWS RELEASE 24-MAR-2020

New study: Cannabis helps fight resistant bacteria

UNIVERSITY OF SOUTHERN DENMARK

Since the discovery of penicillin in 1928 by Sir Alexander Fleming, antibiotics have saved millions of lives from fatal infections world-wide. However, with time bacteria have developed mechanisms to escape the effects of antibiotics – they have become resistant.

With fewer antibiotics available to treat resistant bacterial infections, the possibility of entering a pre-antibiotic era is looming ahead.

Alternative strategies are being explored and helper compounds are attracting attention. Helper compounds are non-antibiotic compounds with the capability of enhancing the efficacy of antibiotics.

How to boost antibiotics

One such helper compound has been suspected to be cannabidiol (CBD); a cannabinoid from the cannabis plant. Now a research team from University of Southern Denmark, has published a scientific study proving the effect of CBD.

Janne Kudsk Klitgaard is Principal Investigator and corresponding author. First author is PhD student Claes Søndergaard Wassmann. The study is published in the journal Scientific Reports.

When we combined CBD and antibiotics, we saw a more powerful effect than when treating with antibiotics alone. So, in order to kill a certain number of bacteria, we needed less antibiotics, they say.

Bacteria clones spread globally

In the study, CBD was used to enhance the effect of the antibiotic bacitracin against Staphylococcus aureus bacteria; a major human pathogen that frequently causes community- and hospital-acquired disease.

Multidrug-resistant clones of this pathogen have spread globally. In some countries, treatment of bacterial infections with these resistant bacteria are difficult and the problem is projected to be an ever-larger problem in the future.

According to the researchers, the combination of CBD and antibiotics may be a novel treatment of infections with antibiotic resistant bacteria.

How do the bacteria die?

Three things happened with the Staphylococcus aureus bacteria, when the researchers treated them with the combination in their study:

The bacteria could no longer divide normally.

The expression of certain key genes (cell division and autolysis genes) in the bacteria was lowered.

The bacterial membrane became unstable.

Anti-resistance must be stopped

According to the researchers, overuse of antibiotics is the main cause of antibiotic resistance.

If we combine an antibiotic with a helper compound, that enhances the effect of the antibiotic, we need less antibiotic to achieve the same effect. This may contribute to the development of fewer resistant bacteria, says Janne Kudsk Klitgaard.

NEWS RELEASE 31-MAR-2020

Coconut oil reduces features of metabolic syndrome in obese females, animal study finds

THE ENDOCRINE SOCIETY

WASHINGTON–Obese females that ate a small amount of coconut oil daily, even as part of a high-fat diet, had decreased features of metabolic syndrome, a cluster of risk factors that raise the chances of developing diabetes, heart disease and stroke, an animal study finds. The study results were accepted for presentation at ENDO 2020, the Endocrine Society’s annual meeting, and will be published in a special supplemental section of the Journal of the Endocrine Society.

“Our controlled experimental study suggests that coconut oil may not be bad for cardiometabolic health, contrary to what previous studies have concluded,” said the study’s lead investigator, Annie Newell-Fugate, D.V.M., Ph.D., an assistant professor at Texas A&M University in College Station, Texas.

Nearly 40% of U.S. adults meet the criteria for obesity, the Centers for Disease Control and Prevention reports. One in five Americans has metabolic syndrome, which is linked partly to obesity, according to the Endocrine Society’s Hormone Health Network. Adding to the problem, Newell-Fugate said, is that the typical Western diet may contain 40% or more fat.

The researchers wanted to learn whether eating a small amount of coconut oil could improve metabolism, despite consumption of a Western-style diet in which 49% of daily calories came from fat. Their study used an animal model of reproductive-age women with obesity and metabolic syndrome: sexually mature, female mini-pigs fed a high-fat, high-fructose diet resembling a Western diet. For eight months, two groups of pigs ate this high-fat diet consisting of 4,500 calories a day, but the groups differed by the type of one saturated fat. One group’s food included 5% animal lard, which Newell-Fugate said some U.S. regions and ethnic cultures commonly use for cooking. The other high-fat diet group received 5% nonorganic coconut oil instead of lard in their food. A third group of pigs ate a low-calorie, lean diet as a control.

Although both groups fed the high-fat diet became obese, the pigs that received coconut oil had lower cholesterol and blood glucose (sugar) levels compared with the pigs that ate the lard-supplemented diet, Newell-Fugate reported. Also, the coconut oil group had less evidence of fatty liver disease and less deep belly fat than the lard group.

“Our research suggests that coconut oil may be used with lifestyle modifications and anti-diabetic drugs to treat metabolic syndrome, at least in women with obesity,” Newell-Fugate said. She added that they do not know if their findings also apply to men.

Coconut oil is available in many grocery stores and could substitute for other saturated fats in small quantities, she suggested. “Substituting one tablespoon of your saturated fat calories per day with coconut oil could result in an improvement in your cardiometabolic health,” Newell-Fugate said.

NEWS RELEASE 2-APR-2020

Researchers find that nicotinamide may help treat fibrotic eye diseases and mitigate vision loss

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

Nicotinamide, a form of vitamin B3, can inhibit aggressive cell transformations during wound healing and may be key to the development of therapies to treat fibrotic eye diseases that impair vision, according to a new Mount Sinai study published on Thursday, April 2, in Stem Cell Reports.

The findings apply to a condition in which cells in the retinal pigment epithelium, a layer that supports the retina, transform and develop the characteristics of more aggressive cells known as mesenchymal cells. The condition can be triggered by aging, diabetes, or injury to the eye. This causes development of fibrous membranes that resemble damaging cells found in retinal scar tissue, and can lead to retinal detachment.

The researchers found that nicotinamide not only inhibits these cell transformations, but can also reverse that cell transition and slow down the development of eye diseases that may lead to vision loss or blindness.

When applying nicotinamide as a therapy to human adult cells in vitro, the researchers found that the vitamin B derivative slowed down the aggressive cellular transformation and could promote the opposite transition, from mesenchymal to epithelial, helping to preserve the cell’s original identity.

“This is the first study that shows how nicotinamide can inhibit invasive wound healing, but also reverse the development of membranes associated with scar tissue,” said Timothy Blenkinsop, PhD, co-lead investigator of the study and Assistant Professor of Cell, Developmental and Regenerative Biology at the Icahn School of Medicine at Mount Sinai. “This discovery helps evolve our understanding of wound healing, as well as good inflammation versus bad inflammation. Good inflammation essentially nudges the system into a regenerative response, while bad inflammation can create harmful scar tissue formation. This is an exciting time to understand how this compound can be used to treat and reverse not only fibrotic diseases of the retina but other diseases too.”

The researchers also identified epigenetic and molecular changes that occur during the cell transition process. Nicotinamide therapy resulted in widespread changes in the DNA sequence of the cells, eliciting changes in more than 40,000 identified chromosomal regions. The scientists observed that nicotinamide was associated with massive reorganization of the cell patterns, especially with inducing enhancer elements that lead the cell stage change in the retina. It activated regulatory elements in cells, including transcriptional factors that are prominent regulators of cell transformation.

Sally Temple, PhD, co-lead investigator of the study and Scientific Director at Neural Stem Cell Institute, said the study paves the way to develop new forms of treatment for patients. “Now we know the epigenetic landscape that is associated with the changes activated by nicotinamide, which gives deeper insights into cell transformations and provides an opportunity to explore a pathway for new therapeutic approaches for any condition or complication associated with wound healing.”

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NEWS RELEASE 6-APR-2020

Compound in fruit peels halts damage and spurs neuronal repair in multiple sclerosis

Ursolic acid, abundant in fruit peels and some herbs, both prevents and repairs neurons in animal models of multiple sclerosis

THOMAS JEFFERSON UNIVERSITY

PHILADELPHIA – Multiple sclerosis (MS), characterized by increasing muscle weakness and paralysis, has a number of treatments that help stall progression of the disease when used early on in the disease. But the current treatments can hardly reverse damage that has already occurred in brain cells called neurons. New research suggests that a compound found in the peels of fruits such as apples and prunes, and some herbs, can reduce further damage to neurons, and also help rebuild the protective sheaths covering neurons, reversing the damage.

“Although the evidence is preliminary – our data is from animal models of disease – it’s encouraging to see a compound that both halts and repairs damage in MS, in the lab,” says Guang-Xian Zhang, PhD, co-senior author and Professor of Neuroscience at the Sidney Kimmel Medical College at Thomas Jefferson University. The study was published in the Proceedings of the National Academy of Sciences (PNAS) on Monday April 6th.

“There is additional work we must do to test the safety of this compound, ursolic acid” says co-senior author A.M. Rostami, MD, PhD, chair of the department of Neurology at the Vickie and Jack Farber Institute for Neuroscience – Jefferson Health. “But this is a great new lead for disease treatment.”

The researchers used a lab-grade purified form of ursolic acid in mice that had established MS disease. “Many experiments have looked at mice in the acute phase, when disease is just starting or at the peak,” says Dr. Zhang. “Instead, we tested whether this compound was effective in chronic disease, once there has already been chronic damage to tissues of central nervous system.”

Drs. Zhang, Rostami, together with first author Yuan Zhang and colleagues used an established mouse model of multiple sclerosis that develops the disease slowly over the course of its life, mimicking human disease. At about day 12, the mouse begins the acute phase of the disease, when signs of MS, partial paralysis, appear, and when currently-available medications are most effective. The researchers, however, started treating mice at day 60, – a far more advanced stage of the disease when chronic tissue damage has been formed in brain and spinal cords, which needs to be repaired and regenerated.

Researchers treated the mice for 60 days, and began to see an improvement at day 20 of treatment. The mice which were paralyzed at the start of the experiment, regained the ability to walk around again, although with weakness, after treatment.

“It’s not a cure, but if we see a similar response in people, it would represent a significant change in quality of life. And most significantly, it’s a reversal, which we really haven’t seen before with other agents at such a late stage of disease,” says Dr. Zhang.

The researchers also investigated just how ursolic acid acted on cells. They observed that it suppressed Th17 cells – a type of immune cell that is one of the main drivers of the pathological autoimmune response in MS. Many currently active therapies appear to suppress Th17. But the Jefferson researchers showed that the compound could activate precursor cells to mature into much needed myelin-sheath-making cells, called oligodendrocytes.

“This maturation effect is the most crucial,” says Dr. Zhang. “Myelin-sheath-making oligodendrocytes are depleted in MS. And the stem cells that produce new oligodentrocytes are dormant and unable to mature. This compound helps activate those stem cells into making new oligodendrocytes, and is likely responsible for the reversal of symptoms we saw.”

The next steps for the investigators include testing the compound for safety. Although ursolic acid is available as a dietary supplement, it could be toxic at high doses. “There are still a number of tests to complete before the first clinical trials,” says Dr. Rostami. “However, we are moving quickly with this promising approach.”

NEWS RELEASE 7-APR-2020

Researchers suggest a special diet against asthma

Study by the University of Bonn proves success of a so-called ketogenic diet

UNIVERSITY OF BONN

Can a special diet help in certain cases of asthma? A new study at the University of Bonn at least points to this conclusion. According to the study, mice that were switched to a so-called ketogenic diet showed significantly reduced inflammation of the respiratory tract. The results are now published in the renowned journal Immunity.

Asthma patients react even to low concentrations of some allergens with severe inflammation of the bronchi. This is also accompanied by increased mucus production, which makes breathing even more difficult. A central role here is played by cells of the innate immune system, which were only discovered a few years ago and are called Innate Lymphoid Cells (ILC). They perform an important protective function in the lungs by regenerating damaged mucous membranes. For this purpose they produce inflammatory messengers from the group of cytokines, which stimulate division of the mucosal cells and promote mucus production.

This mechanism is normally very useful: It allows the body to quickly repair damage caused by pathogens or harmful substances. The mucus then transports the pathogens out of the bronchial tubes and protects the respiratory tract against re-infection. “With asthma, however, the inflammatory reaction is much stronger and longer than normal”, emphasizes Prof. Dr. Christoph Wilhelm from the Institute for Clinical Chemistry and Clinical Pharmacology, who is a member of the Cluster of Excellence ImmunoSensation at the University of Bonn. The consequences are extreme breathing difficulties, which can even be life-threatening.

Rapid reproduction

The ILCs multiply rapidly during this process and produce large amounts of proinflammatory cytokines. Scientists hope that if their division could be slowed down, it may be possible to bring the excessive reaction under control. In fact, the results now published point in exactly this direction. “We have investigated which metabolic processes are active in the ILCs when they switch to reproduction mode,” explains Wilhelm’s colleague Dr. Fotios Karagiannis. “Then we tried to block these metabolic pathways and thereby reduce the speed at which the cells divide.”

Some metabolic pathways were in fact significantly more active in dividing ILCs. They primarily ensure that the cells are supplied with energy and with the building blocks they require for reproduction. The latter include, for example, fatty acids that are needed to make the cell membrane. This forms a thin skin with which cells separate themselves from their surroundings. “Activated ILCs therefore absorb fatty acids from their environment and store them in their interior in small droplets for a short time, before they utilise them for energy or building membranes,” explains Karagiannis.

But what happens if cells are forced to use these fatty acids elsewhere? To answer this question, the researchers put asthmatic mice on a diet that contained mainly fats, but hardly any carbohydrates or proteins. With this diet, also known as a ketogenic diet, the cell metabolism changes: The cells now get the energy they need from burning fat. However, this means that they lack fatty acids, which they need for the formation of new membranes during cell division.

As a consequence, the division activity of the ILCs in the rodents fed a special diet decreased – dramatically: “Normally, contact with allergens increases the number of ILCs in the bronchi fourfold,” says Prof. Wilhelm. “In our experimental animals, however, it remained almost unchanged. Both mucus production and other asthma symptoms decreased accordingly.”

This is not only due to the switch to fats as an alternative energy source and the resulting shortage of fatty acids. The glucose deficiency presumably also directly contributes to the reduced activity of the ILCs. “The prevalence of asthma has increased dramatically over the last few decades. Perhaps this is also related to an increasingly common high-sugar and high-fat diet,” speculates Wilhelm.

The scientists now want to investigate on patients whether a ketogenic diet can prevent asthma attacks. However, this is not completely without long-term risks and should only be carried out in consultation with a doctor. “We are therefore trying to determine which components of the dietary change are responsible for the effect,” explains Wilhelm. “Maybe this will open the door to the development of new drugs.”

It is known that a ketogenic diet can be an effective therapy for some diseases. For instance, patients with certain forms of epilepsy are treated with this method. And the change in diet is also said to help with some tumors – after all, the cells in them also multiply unusually strongly.

NEWS RELEASE 8-APR-2020

Drinking green tea may help with food allergies

SHINSHU UNIVERSITY

Research findings suggest gut microbes can effect allergic immune responses. Tasuku Ogita who has recently joined Shinshu University is an expert on teas and their effects on gut bacteria. In this study, his team looked at green tea and the abundance of Flavonifractor plautii (FP) bacteria found in the gut. FP has been reported to be a part of the catechin metabolism in the intestines. Catechin is an antioxidant found in a variety of foods including green tea, of which 30 to 42% of its dry weight is catechin.

Tasuku Ogita and his team including supervisor Takeshi Shimosato has found that oral administration of FP strongly suppresses the Th2 immune response to food allergies in vivo. The food we eat effects the complex cocktail of different strains of bacteria in the gut. Drinking green tea increases the abundance of FP (Flavonifractor plautii) which suppresses the Th2 immune response. FP is a strain of the Clostridia family of bacteria, which is known to have effects on the immune system, notably inhibiting inflammation. Some Clostridia strains show promise of lowering blood pressure and some are known to be abundant in lean people and not in heavier people, leading researchers to believe they can be used to regulate weight.

Dr. Ogita has successfully cultured FP which took 6 months to accomplish. It is not easy to grow bacteria that grows inside the intestines out of its environment. Dr. Ogita was delighted when he was able to see the “face” of this FP strain under a microscope. A photo of the FP bacteria did not exist because research into its study is in its infancy. Dr. Ogita believes this is the first photo of FP.

Shinshu University is located in Nagano prefecture, known throughout Japan for having a variety of fermented food items with positive health outcomes. Nagano is unusual in that it does not have direct access to an ocean, so the food culture that has developed here has been unique. Due to its mountainous terrain, residents have had to survive long winters without access to the outside world, cultivating a rich food culture of natural preserves including miso and lacto-fermented pickles.

Nowadays, its residents have the best health and highest longevity in Japan, meaning it is likely a great contender for the area with some of the best health lifestyles in the world. Nagano manages to do this with some of the lowest costs for medical care for the elderly in Japan, meaning people live long but are also healthier longer. Researchers at Shinshu University continue to work to study unique foods indigenous to Nagano and Japan, and metabolic processes in the body scientifically to share this knowledge with others around the world with the hope that they too, can benefit from this culture.

There is potential for the FP strains of bacteria to follow in the steps of lactic acid bacteria and bifidobacterium in being added to foods for their desired functionality. At this point more studies are needed to look into the safety of FP before it can be used as an anti-allergy probiotic.

NEWS RELEASE 8-APR-2020

The Lancet Gasteroenterology & Hepatology: First clinical trial finds probiotic treatment with dead bacteria is better than placebo at alleviating symptoms of irritable bowel syndrome

THE LANCET

Probiotic bacteria that have been killed by heat can significantly improve symptoms of irritable bowel syndrome (IBS) compared to placebo, and are not associated with any safety risk, according to a new 12-week, randomised, double-blind, placebo-controlled clinical trial with 443 patients published in The Lancet Gastroenterology & Hepatology journal.

Although they do not know the exact way this potential treatment works, the researchers suggest that these dead bacterial cells are able to stick to cells lining the stomach in the same way that live probiotics do. This may help to strengthen the gut’s barrier against harmful bacteria and toxins, which otherwise may contribute to the symptoms of IBS. They also observed a strong placebo effect, which is common in IBS studies, but the probiotic treatment was still significantly better than placebo.

Previous trials with probiotics to alleviate IBS symptoms have focused on live bacterial strains, with a few having a significant clinical effect, including Bifidobacterium bifidum MIMBb75 [1]. This bacterium is particularly good at sticking to cells in the gut wall, which could explain its effects. The use of live probiotics is considered safe, but they have a limited shelf life. Some bacteria die in storage, so it is not known how many are still alive when people take them. On rare occasions, live probiotics have also been reported to cause severe infections, particularly in people with severe illnesses or compromised immune systems. Non-viable probiotics could therefore be an even safer alternative, with the added advantage of a longer shelf life, even in countries with warm climates.

“To our knowledge, no other dead bacterial strain has been found to significantly improve IBS and its symptoms, but the probiotic we used in this first clinical trial appears to reach or even surpass the effects of the live form,” says Professor Peter Layer from University of Hamburg Teaching Hospital, Germany, who led the research. [2]

Symptoms of IBS include recurrent episodes of abdominal pain, flatulence, a swollen stomach, feeling uncomfortably bloated, pain while defecating, diarrhoea, and constipation. The symptoms can harm patients’ quality of life, and according to previous studies, the effect on quality of life can be even worse in people with chronic diseases [3]. The causes of IBS are not fully known, but the internal lining of the gut is thought to be more permeable in patients with symptoms.

All patients in the new study experienced chronic abdominal pain or discomfort on at least three days in the past three months, with symptoms having started at least six months previously (in accordance with Rome III diagnostic criteria). In addition, the researchers only included patients who experienced abdominal pain on at least two days in the two weeks prior to the start of the study.

They randomly assigned 443 patients to take either two capsules of heat-inactivated Bifidobacterium bifidum MIMBb75, or two placebo capsules, twice daily, for eight weeks. They measured whether abdominal pain improved by at least 30% over eight weeks of treatment, from when they took the first capsule of treatment, and whether all IBS symptoms were significantly relieved at least 50% of the time while the capsules were being taken.

Out of 221 patients who received the probiotic, 74 (34%) experienced an improvement in abdominal pain by at least 30% and a significant alleviation of IBS symptoms at least 50% of the time, compared to 43 (19%) of the 222 patients who received the placebo. This translates to 1.7 times greater treatment success in the probiotic group.

There was no difference in side effects between the groups, and none of the side effects were severe. The most common side effect reported was abdominal pain, which was reported by less than 1% of patients in both groups. 200 (91%) of patients rated the tolerability of treatment as good or very good, compared to 191 (86%) in the placebo group.

The authors highlight the considerable placebo response as a potential limitation of the study, with 19% of patients recording an improvement in symptoms according to the study criteria. However, they point out that a strong placebo response is common in controlled IBS trials. For example, in some studies, over 40% of patients have reported an improvement in IBS symptoms when receiving only a placebo. [4]

“Our results show for the first time that dead or alive, it’s possible to preserve the beneficial effects of some probiotic bacteria,” says co-author Dr Viola Andresen, also from University of Hamburg teaching hospital. “They could be just as effective as live probiotics, as well as even safer, with the added commercial benefit of a longer shelf life.” [2]

Writing in a linked Comment, lead author Nicholas Talley (who was not involved in the study) from the University of Newcastle, Australia, says: “A previous, smaller randomised controlled trial reported that viable B bifidum modestly improved IBS symptoms compared with placebo. Andresen and colleagues’ trial reported a similar benefit of non-viable B bifidum to that observed with viable organisms in terms of effect size. A strength of the study was that all IBS subtypes were included in the analysis, and the inactivated bacterial therapy appeared to benefit the different subgroups.”

NOTES TO EDITORS

NEWS RELEASE 7-APR-2020

Treatment relieves depression in 90% of participants in small study

STANFORD MEDICINE

A new form of magnetic brain stimulation rapidly relieved symptoms of severe depression in 90% of participants in a small study conducted by researchers at the Stanford University School of Medicine.

The researchers are conducting a larger, double-blinded trial in which half the participants are receiving fake treatment. The researchers are optimistic the second trial will prove to be similarly effective in treating people whose condition hasn’t improved with medication, talk therapy or other forms of electromagnetic stimulation.

The treatment is called Stanford Accelerated Intelligent Neuromodulation Therapy, or SAINT. It is a form of transcranial magnetic stimulation, which is approved by the Food and Drug Administration for treatment of depression. The researchers reported that the therapy improves on current FDA-approved protocols by increasing the number of magnetic pulses, speeding up the pace of the treatment and targeting the pulses according to each individual’s neurocircuitry.

Before undergoing the therapy, all 21 study participants were severely depressed, according to several diagnostic tests for depression. Afterward, 19 of them scored within the nondepressed range. Although all of the participants had suicidal thoughts before the therapy, none of them reported having suicidal thoughts after treatment. All 21 participants had previously not experienced improvements with medications, FDA-approved transcranial magnetic stimulation or electroconvulsive therapy.

The only side effects of the new therapy were fatigue and some discomfort during treatment, the study reported. The results will be published online April 6 in the American Journal of Psychiatry.

“There’s never been a therapy for treatment-resistant depression that’s broken 55% remission rates in open-label testing,” said Nolan Williams, MD, assistant professor of psychiatry and behavioral sciences and a senior author of the study. “Electroconvulsive therapy is thought to be the gold standard, but it has only an average 48% remission rate in treatment-resistant depression. No one expected these kinds of results.”

Calming the brain chatter

When Deirdre Lehman, 60, woke up the morning of June 30, 2018, she said she was hit by “a tsunami of darkness.” Lehman had struggled with bipolar disorder all her adult life, but with medications and psychotherapy her mood had been stable for 15 years.

“There was a constant chattering in my brain: It was my own voice talking about depression, agony, hopelessness,” she said. “I told my husband, ‘I’m going down and I’m heading toward suicide.’ There seemed to be no other option.”

Lehman’s psychiatrist had heard of the SAINT study and referred her to Stanford. After researchers pinpointed the spot in her brain that would benefit from stimulation, Lehman underwent the therapy.

“By the third round, the chatter started to ease,” she said. “By lunch, I could look my husband in the eye. With each session, the chatter got less and less until it was completely quiet.

“That was the most peace there’s been in my brain since I was 16 and started down the path to bipolar disorder.”

In transcranial magnetic stimulation, electric currents from a magnetic coil placed on the scalp excite a region of the brain implicated in depression. The treatment, as approved by the FDA, requires six weeks of once-daily sessions. Only about half of patients who undergo this treatment improve, and only about a third experience remission from depression.

Stanford researchers hypothesized that some modifications to transcranial magnetic stimulation could improve its effectiveness. Studies had suggested that a stronger dose, of 1,800 pulses per session instead of 600, would be more effective. The researchers were cautiously optimistic of the safety of the treatment, as that dose of stimulation had been used without harm in other forms of brain stimulation for neurological disorders, such as Parkinson’s disease.

Other studies suggested that accelerating the treatment would help relieve patients’ depression more rapidly. With SAINT, study participants underwent 10 sessions per day of 10-minute treatments, with 50-minute breaks in between. After a day of therapy, Lehman’s mood score indicated she was no longer depressed; it took up to five days for other participants. On average, three days of the therapy were enough for participants to have relief from depression.

“The less treatment-resistant participants are, the longer the treatment lasts,” said postdoctoral scholar Eleanor Cole, PhD, a lead author of the study.

Strengthening a weak connection

The researchers also conjectured that targeting the stimulation more precisely would improve the treatment’s effectiveness. In transcranial magnetic stimulation, the treatment is aimed at the location where most people’s dorsolateral prefrontal cortex lies. This region regulates executive functions, such as selecting appropriate memories and inhibiting inappropriate responses.

For SAINT, the researchers used magnetic-resonance imaging of brain activity to locate not only the dorsolateral prefrontal cortex, but a particular subregion within it. They pinpointed the subregion in each participant that has a relationship with the subgenual cingulate, a part of brain that is overactive in people experiencing depression.

In people who are depressed, the connection between the two regions is weak, and the subgenual cingulate becomes overactive, said Keith Sudheimer, PhD, clinical assistant professor of psychiatry and a senior author of the study. Stimulating the subregion of the dorsolateral prefrontal cortex reduces activity in the subgenual cingulate, he said.

To test safety, the researchers evaluated the participants’ cognitive function before and after treatment. They found no negative side effects; in fact, they discovered that the participants’ ability to switch between mental tasks and to solve problems had improved — a typical outcome for people who are no longer depressed.

One month after the therapy, 60% of participants were still in remission from depression. Follow-up studies are underway to determine the duration of the antidepressant effects.

The researchers plan to study the effectiveness of SAINT on other conditions, such as obsessive-compulsive disorder, addiction and autism spectrum disorders.

‘Resilient and stable’

The depression Lehman woke up to almost two years ago was the worst episode she had ever experienced. Today, she said, she is happy and calm.

Since undergoing SAINT treatment, she has completed a bachelor’s degree at the University of California-Santa Barbara; she had dropped out as a young woman when her bipolar symptoms overwhelmed her studies.

“I used to cry over the slightest thing,” she said. “But when bad things happen now, I’m just resilient and stable. I’m in a much more peaceful state of mind, able to enjoy the positive things in life with the energy to get things done.”

NEWS RELEASE 13-APR-2020

Exercise restores youthful properties to muscle stem cells of old mice in Stanford study

STANFORD MEDICINE

A nightly jaunt on the exercise wheel enhances muscle-repair capabilities in old mice, according to a new study by researchers at Stanford School of Medicine.

Only older mice saw this benefit, which the researchers found is due to the rejuvenation of the animals’ muscle stem cells.

“The effect in old animals is very significant,” said Thomas Rando, MD, PhD, professor of neurology and neurological sciences and director of Stanford’s Glenn Center for the Biology of Aging. “We found that regular exercise restores youthfulness to tissue repair. Their muscle stem cells start to look and behave like those of much younger animals.”

The researchers also identified a molecular pathway involved in turning back the clock on the cells. Drugs that manipulate the pathway might be an effective substitute for exercise, they suggest.

Rando is the senior author of the study, which will be published April 13 in Nature Metabolism. Medical student Jamie Brett, PhD, postdoctoral scholar Marina Arjona, PhD, and visiting scholar Mika Ikeda, PhD, are the lead authors.

Unlike embryonic or induced pluripotent stem cells, which can give rise to any tissue in the body, tissue-specific stem cells are restricted in their potential. Muscle stem cells wait in the wings along the muscle fibers in a resting state known as quiescence until called upon to repair damage.

“Studies conducted by us and others have shown that tissue regeneration decreases with age, and that this is due to declining function in adult stem cells,” Rando said. “Many researchers are looking for a way to restore youthfulness.”

Benefits of lifestyle adjustments

While no researchers have discovered a reliable fountain of youth, it’s well known that certain lifestyle adjustments can be beneficial.

“Exercise is known to reduce the risk of a wide variety of age-related problems, including cardiovascular disease, cancer and perhaps even Alzheimer’s disease,” Rando said. “There’s a lot of interest in understanding how exercise confers these health benefits.”

In particular, the researchers wanted to know whether and how voluntary exercise affects the function of muscle stem cells in mice. They gave mice that were about 20 months old, the equivalent of being 60-70 years old in humans, and mice that were 3 to 4 months old, the equivalent of 20- to 30-year-old humans, access to an exercise wheel and allowed them to run at will. Young mice averaged about 10 kilometers each night, and the older mice covered about 5 kilometers. Two other groups of young and old mice were given wheels that didn’t rotate to serve as controls.

“The animals were exercising at the intensity levels at which they were comfortable,” Rando said, “much like what people do for their own health. This is a less stressful situation than resistance training or intense endurance exercise, which may themselves affect muscle stem cell function.” Subsequent analysis showed that the muscle stem cells of the exercising animals remained quiescent, and that the animals did not develop significant numbers of new muscle fibers in response to the exercise.

After three weeks of nightly aerobics for the active groups, the researchers compared the ability of the animals to repair muscle damage. They found that, as expected, the aged, sedentary mice were significantly less able to repair muscle damage than younger sedentary mice. However, the older animals that had exercised regularly were significantly better at repairing muscle damage than were their counterparts that did not exercise. This exercise benefit was not observed in the younger animals.

Similar results were obtained when muscle stem cells from older mice that had exercised were transplanted into younger mice. The stem cells from the exercising animals contributed more to the repair process than did those from their sedentary peers.

Benefit of young blood

The researchers also showed that injecting blood from an old mouse that had exercised into an old mouse that hadn’t conferred a similar benefit in stem cell function, suggesting that exercise simulates the production of some factors that then circulate in the blood and enhance the function of older stem cells.

“That’s really fascinating,” Rando said, noting that the result mirrors those from earlier studies jointly conducted by him and Tony Wyss-Coray, PhD, a professor of neurology and neurological sciences at the School of Medicine, indicating that blood from a young mouse appears to somehow enhance the tissue-specific stem cells in an older animal.

Further studies indicated that the exercise-induced rejuvenation observed by the researchers could be mimicked by increasing the expression of a signaling molecule called cyclin D1, which is involved in rousing resting muscle stem cells in response to damage. The discovery suggests that it may one day be possible to artificially activate this pathway to keep aging muscle stem cells functioning at their youthful best.

“If we could develop a drug that mimics this effect, we may be able to experience the benefit without having to do months of exercise,” Rando said.

 

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