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262 APCNO 26 MAR 2019

262APCNO14MAR2019

262APCNO14MAR2019

Report # 262

Release Date: 26 MAR 2019

Draft Report Compiled by

Ralph Turchiano

www.clinicalnews.org

 

In this issue:

  1. Is prenatal vitamin use by moms associated with risk for autism spectrum disorder recurrence in young siblings?
  2. New study shows red raspberries may help with glucose control in people with pre-diabetes
  3. Few kids’ multivitamin products supply recommended daily vitamin D dose
  4. Alzheimer’s-like symptoms reversed in mice, USC researchers say
  5. Bedtime protein for bigger gains? Here’s the scoop
  6. NUS study: Eating mushrooms may reduce the risk of cognitive decline
  7. Blood pressure control is beneficial, is it not?
  8. Vitamin B3 analogue boosts production of blood cells
  9. Rice U. study highlights danger of vitamin B12 deficiency
  10. Avocado seed extract shows promise as anti-inflammatory compound
  11. Inactive ingredients in pills and capsules may cause allergic, adverse reactions
  12. Pure Omega-3 prescription drug markedly reduces first, repeat and total CV events
  13. Healthy fats improve nerve function in obese mice
  14. Scientists identify compounds in coffee which may inhibit prostate cancer
  15. Green tea cuts obesity, health risks in mice
  16. Fountain of youth for heart health may lie in the gut
  17. Active substance from plant slows down aggressive eye cancer
  18. New research shows people with PAD could have an omega-3 deficiency

 

 

PUBLIC RELEASE: 27-FEB-2019

Is prenatal vitamin use by moms associated with risk for autism spectrum disorder recurrence in young siblings?

JAMA PSYCHIATRY

Bottom Line: This study examined whether prenatal vitamin use by mothers was associated with autism spectrum disorder (ASD) recurrence in high-risk families. The study included 241 children who were selected because a sibling was diagnosed with ASD. Mothers reported their use of prenatal vitamins during pregnancy. While most mothers reported taking prenatal vitamins while pregnant, only 87 (36 percent) mothers met the recommendations to take prenatal vitamins in the six months before pregnancy. Researchers report that children whose mothers had taken prenatal vitamins during the first month of pregnancy appeared less likely to be diagnosed with ASD when compared with children whose mothers hadn’t taken prenatal vitamins during that time. The proportion of children with ASD among mothers who took prenatal vitamins in the first month of pregnancy was 14.1 percent (18 children) compared with 32.7 percent (37 children) among those whose mothers didn’t take prenatal vitamins during that time. One limitation is that this study was observational, which means there may have been differences between the two groups that weren’t accounted for during the analysis, even though the investigators accounted for many factors. Another limitation is the study’s relatively small sample size. This study is important because there have been conflicting studies about whether maternal prenatal vitamin use is associated with a lower risk of ASD. More research is needed to confirm the associations observed in this study.

Authors: Rebecca J. Schmidt, Ph.D., of the University of California, Davis, and coauthors

(doi:10.1001/jamapsychiatry.2018.3901)

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

New study shows red raspberries may help with glucose control in people with pre-diabetes

ILLINOIS INSTITUTE OF TECHNOLOGY

Chicago, IL – February 25, 2019 – A study released today from the Illinois Institute of Technology shows the benefits of including red raspberries in the diet of individuals with pre-diabetes and insulin resistance.

According to the Centers for Disease Control and Prevention (CDC), an estimated 34 percent of American adults, around 84.1 million in all, had prediabetes in 2015. Patients with prediabetes are at higher risk for a number of conditions – including developing type 2 diabetes, cardiovascular disease and Alzheimer’s disease.

The study, published in Obesity, investigated the effects of red raspberries in a group of people at-risk for diabetes who were overweight or obese and presented with prediabetes and insulin resistance. A metabolically healthy control group was also included in the study for reference.

Using a randomized, controlled, acute study design, 32 adults between the ages of 20-60 years had their blood tested over a 24-hour period after eating breakfast on three separate days. The three breakfast meals were similar in calories and macronutrients, but differed in the amount of frozen red raspberries – one meal contained no raspberries, one contained one cup of raspberries and one contained two cups of raspberries.

The results showed that as the amount of raspberry intake increased, individuals at risk for diabetes needed less insulin to manage their blood glucose. When two cups of red raspberries were included in the meal, glucose concentrations were lower compared to the meal with no red raspberries. The data suggests that simple inclusion of certain fruits, such as red raspberries with meals, can have glucose lowering benefits with indications of improvements in insulin responses. These effects are particularly important for people who are overweight or obese with pre-diabetes.

“People at risk for diabetes are often told to not eat fruit because of their sugar content. However, certain fruits – such as red raspberries – not only provide essential micronutrients, but also components such as anthocyanins, which give them their red color, ellagitannins and fibers that have anti-diabetic actions,” said Britt Burton-Freeman, Ph.D., director, Center for Nutrition Research at Illinois Tech. “For people who are at risk for diabetes, cardiovascular disease and other health risks, knowing what foods have protective benefits and working them into your diet now can be an important strategy for slowing or reversing progression to disease.”

PUBLIC RELEASE: 25-FEB-2019

Few kids’ multivitamin products supply recommended daily vitamin D dose

And some supplements specifically ‘for bones’ contain very low levels, survey shows

BMJ

Few multivitamin products for children supply the recommended dose of 400 IU a day of vitamin D, suggest the results of a survey of 91 different products, published online in the Archives of Disease in Childhood.

Supplements containing only vitamin D or labelled specifically ‘for healthy bones’ typically had a higher vitamin D content, although some products contained very low levels of the vitamin.

Low levels of vitamin D are common in children in the UK, particularly during the winter. Vitamin D deficiency can lead to rickets and abnormally low levels of calcium in the blood (hypocalcaemia)–conditions that can be prevented by taking vitamin D supplements.

In 2016, Public Health England recommended a daily dose of 400 IU (10 ug) all year round for all 1-4 year olds, and during the autumn and winter months for adults and children over the age of 4.

The Healthy Start scheme, a public health initiative for low income families in England, provides free multivitamins. But these products contain only 300 IU per day of vitamin D, prompting the researchers to see if other children’s multivitamins sold in the UK might contain less than the recommended amount.

In September 2018, they searched the websites of nine UK supermarkets and high street health product retailers, looking for multivitamins aimed at children under the age of 12.

A product was considered a multivitamin if the packaging or manufacturer’s website included the word ‘multivitamin’ or a version of this, or if more than one vitamin was named.

They also looked at products labelled as a vitamin D supplement, or which suggested they could help with ‘healthy bones’.

If a dose range was advised, they recorded the highest amount, to quantify the daily amount of vitamin D provided.

The researchers found 67 multivitamins, made by 24 different manufacturers, and 24 vitamin D/healthy bones products aimed at children under the age of 12.

The daily vitamin D dose in the multivitamins surveyed ranged from 0 to 800 IU.

Only one multivitamin was suitable for use from birth, supplying 200 IU/day of vitamin D, while for children over 6 months, only between a quarter and a third (25-36%) of the available products supplied at least 400 IU/day.

Some of the products giving a dose range would only supply the recommended vitamin D level at the highest dose.

The vitamin D/healthy bones products supplied between 50 and 1000 IU of vitamin D a day. Six were suitable for use from birth, five of which contained 340-400 IU of vitamin D.

The vitamin D content of these types of supplement was typically higher than that of multivitamins: nearly two thirds (57-67%) contained at least 400 IU/day. But one product labelled as ‘for bones and relaxation’ contained only 50 IU/day of vitamin D.

The researchers point out that their survey was limited to supplements sold by UK retailers, and many other supplements are available from online retailers, including imported products and fortified food products.

But because multivitamins are classed as food products, under European Union regulations, the permissible vitamin D content can range from 20% below, to 50% above, the amount stated on the label, they say.

“There is a wide range of both multivitamins and vitamin D supplements available for children in the UK, yet most of these do not provide the recommended 400 IU/day,” they write.

To obtain this, children would either have to take over the recommended dose, which may increase the risk of toxicity from the other components, or they would have to take a combination of vitamin D and multivitamins, which is more expensive, explain the researchers.

Parents and caregivers need to check that the multivitamins they buy for children contain at least 400 IU/day, they advise.

PUBLIC RELEASE: 6-MAR-2019

Alzheimer’s-like symptoms reversed in mice, USC researchers say

Special diet with compounds contained in green tea and carrots restored working memory

UNIVERSITY OF SOUTHERN CALIFORNIA

A diet containing compounds found in green tea and carrots reversed Alzheimer’s-like symptoms in mice genetically programmed to develop the disease, USC researchers say.

Researchers emphasize that the study, recently published in the Journal of Biological Chemistry, was in mice, and many mouse discoveries never translate into human treatments. Nevertheless, the findings lend credence to the idea that certain readily available, plant-based supplements might offer protection against dementia in humans.

“You don’t have to wait 10 to 12 years for a designer drug to make it to market; you can make these dietary changes today,” said senior author Terrence Town, a professor of physiology and neuroscience at the Keck School of Medicine of USC’s Zilkha Neurogenetic Institute. “I find that very encouraging.”

What’s more, the study supports the idea that combination therapy, rather than a single magic bullet, may offer the best approach to treating the 5.7 million Americans living with Alzheimer’s. Combination treatment is already the standard of care for diseases such as cancer, HIV infection and rheumatoid arthritis.

For this study, the researchers took a look at two compounds: EGCG, or epigallocatechin-3-gallate, a key ingredient in green tea, and FA, or ferulic acid, which is found in carrots, tomatoes, rice, wheat and oats.

The researchers randomly assigned 32 mice with Alzheimer’s-like symptoms to one of four groups with an equal number of males and females. For comparison, each group also contained an equal number of healthy mice. For three months, the mice consumed a combination of EGCG and FA, or EGCG or FA only, or a placebo. The dosage was 30 mg per kilogram of body weight–a dosage well-tolerated by humans and easily consumed as part of a healthy, plant-based diet or in the form supplements.

Before and after the three-month special diet, scientists ran the mice through a battery of neuropsychological tests that are roughly analogous to the thinking and memory tests that assess dementia in humans. Of particular note was a maze in the shape of a Y, which tests a mouse’s spatial working memory–a skill that humans use to find their way out of a building.

Healthy mice instinctively explore each arm of the Y maze, looking for food or a route to escape and entering the three arms in sequence more often than by chance alone. Impaired mice can’t do this as well as their mentally healthy counterparts.

“After three months, combination treatment completely restored working memory and the Alzheimer’s mice performed just as well as the healthy comparison mice,” Town said.

How did it work? Town says one mechanism appeared to be the substances’ ability to prevent amyloid precursor proteins from breaking up into the smaller proteins called amyloid beta that gum up Alzheimer patients’ brains. In addition, the compounds appeared to reduce neuroinflammation and oxidative stress in the brain–key aspects of Alzheimer’s pathology in humans.

Town said he and his lab will continue exploring combination treatment, with a focus on plant-derived substances that inhibit production of the sticky amyloid beta plaques.

PUBLIC RELEASE: 6-MAR-2019

Bedtime protein for bigger gains? Here’s the scoop

Downing a casein shake just before sleep increases muscle mass and strength gains from resistance training, without ‘making you fat’ — but is the effect any different to your regular post-workout protein supplement?

FRONTIERS

Drinking a casein shake just before overnight sleep increases gains in muscle mass and strength in response to resistance exercise. But to date, no study has directly addressed whether this effect is due to increased total protein intake only, or if a bedtime beverage is better.

According to a review published in Frontiers in Nutrition, existing findings nevertheless suggest that overnight sleep is a unique nutritional window for boosting muscle gains – while late-night protein calories needn’t increase body fat.

Casein point: Snijders’ seminal study

“Several one-night studies have shown that pre-sleep protein intake increases muscle protein synthesis during overnight sleep in young adults” says lead author Dr. Tim Snijders, Assistant Professor at Maastricht University. “These have fueled the idea that over a longer period, a pre-sleep protein supplement can maximize the strength and muscle mass gains during regular resistance exercise training.”

Snijders’ 2015 study is the most compelling demonstration to date for this.

His team put 44 healthy young men on a 12-week lifting program. Half were given a nightly pre-sleep protein shake with about 30g of casein and 15 grams of carbs, while the other half got an energy-free drink.

The training was effective – both groups ended with a bigger squat (one rep max) and bigger quads – but the protein-before-bed group gained significantly more muscle strength and size.

Is pre-sleep protein consumption better?

But are muscle gains boosted by pre-sleep protein per se, or just higher total intake of protein and calories?

Just one study has attempted – unsuccessfully – to test this question. It showed that fat-free mass gains over 8 weeks of unaltered training in regular lifters were greater (+1.2 kg vs +0.4 kg) with a nightly casein supplement, compared to the same supplement taken in the morning. The difference was not statistically significant however, perhaps because there were only 26 participants.

“Based on our own studies, we calculated that a huge number of participants would be needed to prove whether a difference might exist in response to pre-sleep protein, versus protein intake at other times of the day,” explains Snijders.

However, there are already numerous indirect indicators that pre-sleep protein specifically is beneficial for healthy young lifters.

Sleep is a unique opportunity for muscle recovery and growth

Fundamentally, pre-sleep protein can be used to improve protein intake distribution over the day, says Snijders.

Muscles can only grow and repair themselves when the right building blocks – amino acids from protein – are available in the blood. But unlike blood glucose, the body does not store and release amino acids to maintain near-constant circulating levels.

“A survey of over 500 athletes found they were typically consuming at total of more than 1.2g protein per kilo of bodyweight across three main meals, but only a paltry 7g of protein as an evening snack. As a result, lower levels of amino acids would be available for muscle growth during overnight sleep.”

But if pre-sleep protein consumption allows muscles to cram in more amino acids at night, will they simply use less during the day? Apparently not, claims Snijders.

“The muscle-building effects of protein supplementation at each meal seem to be additive. In one study we found that the consumption of ample amounts of protein (60g whey) before overnight sleep did not alter the muscle protein synthetic response to a high-protein breakfast the following morning.

“What’s more, others have shown that adding a protein supplement at bedtime does not affect appetite the following morning – so it is unlikely to compromise total protein or calorie intake.”

Bedtime protein won’t ‘make you fat’ or ruin your sleep

While the case for pre-sleep protein remains preliminary, is there any harm in trying it? After all, it does involve consuming calories just before a long period of inactivity.

The evidence is sparse, but encouraging.

“In the 8-week morning vs evening casein study, the additional consumption of protein calories did not result in any increase in fat mass despite the fact that exercise volume did not change,” reports Snijders. “But again, these results should be interpreted with caution due to the low number of volunteers included.

“Supporting this, another group found in 11 young active men that a pre-sleep casein shake actually increased the rate of fat burning the following day. This might be because casein ingestion reduces the insulin response to subsequent meals, which pushes your body to use more fat.”

Based on the results of these studies at least, pre-bed protein consumption, especially casein, doesn’t appear to ‘make you fat.’ Indeed, it appears to actually increase fat metabolism.

Finally, pre-sleep protein may be what keeps Snijders up at night – but it won’t stop you getting your well-earned rest.

“It has been consistently shown that pre-sleep protein ingestion has no effect on sleep onset latency or sleep quality.”

In conclusion: we don’t yet have conclusive evidence for adding pre-sleep protein supplement to your fitness regime: but it’s worth a try – and it’s worth further research.

PUBLIC RELEASE: 12-MAR-2019

NUS study: Eating mushrooms may reduce the risk of cognitive decline

Researchers found seniors who ate more than 300 grams of cooked mushrooms a week were half as likely to have mild cognitive impairment

NATIONAL UNIVERSITY OF SINGAPORE

A team from the Department of Psychological Medicine and Department of Biochemistry at the Yong Loo Lin School of Medicine at the National University of Singapore (NUS) has found that seniors who consume more than two standard portions of mushrooms weekly may have 50 per cent reduced odds of having mild cognitive impairment (MCI).

A portion was defined as three quarters of a cup of cooked mushrooms with an average weight of around 150 grams. Two portions would be equivalent to approximately half a plate. While the portion sizes act as a guideline, it was shown that even one small portion of mushrooms a week may still be beneficial to reduce chances of MCI.

“This correlation is surprising and encouraging. It seems that a commonly available single ingredient could have a dramatic effect on cognitive decline,” said Assistant Professor Lei Feng, who is from the NUS Department of Psychological Medicine, and the lead author of this work.

The six-year study, which was conducted from 2011 to 2017, collected data from more than 600 Chinese seniors over the age of 60 living in Singapore. The research was carried out with support from the Life Sciences Institute and the Mind Science Centre at NUS, as well as the Singapore Ministry of Health’s National Medical Research Council. The results were published online in the Journal of Alzheimer’s Disease on 12 March 2019.

Determining MCI in seniors

MCI is typically viewed as the stage between the cognitive decline of normal ageing and the more serious decline of dementia. Seniors afflicted with MCI often display some form of memory loss or forgetfulness and may also show deficit on other cognitive function such as language, attention and visuospatial abilities. However, the changes can be subtle, as they do not experience disabling cognitive deficits that affect everyday life activities, which is characteristic of Alzheimer’s and other forms of dementia.

“People with MCI are still able to carry out their normal daily activities. So, what we had to determine in this study is whether these seniors had poorer performance on standard neuropsychologist tests than other people of the same age and education background,” explained Asst Prof Feng. “Neuropsychological tests are specifically designed tasks that can measure various aspects of a person’s cognitive abilities. In fact, some of the tests we used in this study are adopted from commonly used IQ test battery, the Wechsler Adult Intelligence Scale (WAIS).”

As such, the researchers conducted extensive interviews and tests with the senior citizens to determine an accurate diagnosis. “The interview takes into account demographic information, medical history, psychological factors, and dietary habits. A nurse will measure blood pressure, weight, height, handgrip, and walking speed. They will also do a simple screen test on cognition, depression, anxiety,” said Asst Prof Feng.

After this, a two-hour standard neuropsychological assessment was performed, along with a dementia rating. The overall results of these tests were discussed in depth with expert psychiatrists involved in the study to get a diagnostic consensus.

Mushrooms and cognitive impairment

Six commonly consumed mushrooms in Singapore were referenced in the study. They were golden, oyster, shiitake and white button mushrooms, as well as dried and canned mushrooms. However, it is likely that other mushrooms not referenced would also have beneficial effects.

The researchers believe the reason for the reduced prevalence of MCI in mushroom eaters may be down to a specific compound found in almost all varieties. “We’re very interested in a compound called ergothioneine (ET),” said Dr Irwin Cheah, Senior Research Fellow at the NUS Department of Biochemistry. “ET is a unique antioxidant and anti-inflammatory which humans are unable to synthesise on their own. But it can be obtained from dietary sources, one of the main ones being mushrooms.”

An earlier study by the team on elderly Singaporeans revealed that plasma levels of ET in participants with MCI were significantly lower than age-matched healthy individuals. The work, which was published in the journal Biochemical and Biophysical Research Communicationsin 2016, led to the belief that a deficiency in ET may be a risk factor for neurodegeneration, and increasing ET intake through mushroom consumption might possibly promote cognitive health.

Other compounds contained within mushrooms may also be advantageous for decreasing the risk of cognitive decline. Certain hericenones, erinacines, scabronines and dictyophorines may promote the synthesis of nerve growth factors. Bioactive compounds in mushrooms may also protect the brain from neurodegeneration by inhibiting production of beta amyloid and phosphorylated tau, and acetylcholinesterase.

Next steps

The potential next stage of research for the team is to perform a randomised controlled trial with the pure compound of ET and other plant-based ingredients, such as L-theanine and catechins from tea leaves, to determine the efficacy of such phytonutrients in delaying cognitive decline. Such interventional studies will lead to more robust conclusion on causal relationship. In addition, Asst Prof Feng and his team also hope to identify other dietary factors that could be associated with healthy brain ageing and reduced risk of age-related conditions in the future.

PUBLIC RELEASE: 11-MAR-2019

Blood pressure control is beneficial, is it not?

New findings on blood pressure control in older adults

CHARITÉ – UNIVERSITÄTSMEDIZIN BERLIN

Until recently, physicians had generally assumed that older adults benefit from keeping their blood pressure below 140/90 mmHg. However, researchers from Charité – Universitätsmedizin Berlin have now found that this assumption does not apply to all patients with high blood pressure. The reality is, in fact, quite the opposite: lower blood pressure is associated with an increased risk of death in adults over the age of 80, and in adults who have previously had a heart attack or stroke. Results from this study have been published in the European Heart Journal*.

Approximately 70 to 80 percent of 70-year-olds have high blood pressure – a condition which, over the long term, can lead to cardiovascular diseases such as heart attacks and stroke. Physicians refer to professional guidelines when deciding how to treat a person with high blood pressure. In order to protect against cardiovascular disease in people over the age of 65, the European guidelines recommend a target blood pressure of below 140/90 mmHg. While the same target values apply in persons over the age of 80, additional factors, such as an individual patient’s comorbidities, should be taken into account. Professional associations in the US even go so far as to recommend a target value of under 130/80 mmHg for all patients aged over 65. The scientific debate over which target values produce the best outcomes in older patients with high blood pressure remains ongoing.

Using an observational study design, Charité researchers were able to show that blood pressure-lowering (antihypertensive) drugs administered to achieve target levels of under 140/90 mmHg do not always have a protective effect. Results were even more pronounced for target levels below 130/80 mmHg. These findings are based on epidemiological data from more than 1,600 men and women, all of whom were receiving treatment for high blood pressure and were aged 70 or over at the beginning of the study in 2009. The researchers found that mortality was 40 percent higher in 80-year-olds with blood pressure levels below 140/90 mmHg than in those whose blood pressure exceeded 140/90 mmHg. Observations were similar in participants who had previously had a heart attack or stroke. Notably, mortality was 61 percent higher among patients whose blood pressure was under 140/90 mmHg than in patients whose blood pressure remained above this level despite antihypertensive treatment. “Our results show clearly that, within these groups of patients, antihypertensive treatment should be adjusted based on the needs of the individual,” explains the study’s first author, Dr. Antonios Douros of Charité’s Institute of Clinical Pharmacology and Toxicology. He adds: “We should move away from the blanket approach of applying the recommendations of professional associations to all groups of patients.”

The epidemiological data used were collected as part of the Berlin Initiative Study (BIS), which is led by Prof. Dr. Elke Schäffner, Deputy Director of Charité’s Institute of Public Health. At two-yearly intervals, researchers asked participants about their medical conditions and medicines, measured their blood pressure and kidney function, and analyzed both blood and urine samples. After six years, the data were statistically analyzed to determine whether and to what extent blood pressure might have an effect on mortality. This analysis took into account other potentially relevant factors, such as gender, body mass index, smoking status, alcohol consumption, diabetes and the number of antihypertensive drugs. “As a next step, we want to study which groups of patients actually benefit from antihypertensive treatment,” remarks Prof. Schäffner.

PUBLIC RELEASE: 7-MAR-2019

Vitamin B3 analogue boosts production of blood cells

ECOLE POLYTECHNIQUE FÉDÉRALE DE LAUSANNE

Stem cell-based therapies are becoming more and more common, especially in the treatment of blood cancers like lymphoma and leukemia. In these cases, the patient’s cancerous blood stem cells are removed and replaced with new, healthy ones. However, up to a quarter of cases end in death because replenishing of blood cells is too slow.

One solution to this is to boost the divisions of so-called hematopoietic (“blood-making”) stem cells (HSCs); these are the stem cells that produce the various types of blood cells in our bodies – red, white etc. So, pushing HSCs to divide faster would be ideal; the question is how.

We already know that what causes HSCs to slow down is stress: having to reconstitute the entire blood-cell supply system can be overwhelming. In terms of biology, this stress causes increased activity in mitochondria, the energy-producing organelles of the cell.

To meet the high demands of rebuilding blood cells, the mitochondria of the HSCs increase a process called “oxidative phosphorylation”, which generates fuel for the cell. But this has cost: boosting the activity of mitochondria causes HSCs to age prematurely.

Drawing on this, a team of scientists led by Olaia Naveiras at EPFL and Nicola Vannini at the Ludwig Institute for Cancer Research Lausanne Branch have now found that an analogue of vitamin B3, nicotinamide riboside, can increase HSCs and boost their activity. The study, which also involved labs from EPFL’s Institute of Bioengineering, and the University hospital of Lausanne (CHUV) has significant implications for stem-cell therapy patients, especially since nicotinamide riboside can be taken as a dietary supplement and still have such effects.

When they studied the effects of nicotinamide riboside in vitro the researchers found that exposing human and mouse HSCs to it improves their function and increases mitochondrial recycling – the process by which stressed-out mitochondria get cleared out to make way for fresh ones.

The researchers found that adding nicotinamide riboside to the diet of mice that had undergone an irradiation procedure that eliminates their blood cells – modeling radiotherapy – improved their survival by 80% and accelerated blood recovery. In immunodeficient mice, nicotinamide riboside increased the production of white blood cells (leucocytes).

What all this translates into is a significant improvement in the ability of HSCs to divide and produce new blood cells. The study shows, for the first time, that nicotinamide riboside as a dietary supplement can have a significant positive effect on preventing blood-recovery problems in cancer patients, even after chemo- or radio-therapy.

“We expect nicotinamide riboside and other mitochondrial modulators to become a complementary approach for increasing stem cell fitness and accelerating blood production, either through dietary supplementation or pharmacological administration,” says Naveiras.

###

Professor Naveiras’ lab is part of the Swiss Institute for Experimental Cancer Research (ISREC) within the School of Life Sciences at EPFL. ISREC@EPFL is part of the Swiss Cancer Center Léman (SCCL), a multidisciplinary alliance pursuing fundamental, translational, and clinical cancer research. The SCCL founding members are the Lausanne University Hospital (CHUV), the Geneva University Hospitals (HUG), the universities of Lausanne (UNIL) and Geneva (UNIGE), and EPFL. Professor Naveiras is also a consulting hematologist (Cheffe de Clinique) at the Hematology Service of CHUV.

PUBLIC RELEASE: 13-MAR-2019

Rice U. study highlights danger of vitamin B12 deficiency

Researchers finds first direct link between low-B12 diet, increased risk of infection

RICE UNIVERSITY

HOUSTON — (March 13, 2019) — Using roundworms, one of Earth’s simplest animals, Rice University bioscientists have found the first direct link between a diet with too little vitamin B12 and an increased risk of infection by two potentially deadly pathogens.

Despite their simplicity, 1-millimeter-long nematodes called Caenorhabditis elegans (C. elegans) share an important limitation with humans: They cannot make B12 and must get all they need from their diet. In a study published today in PLOS Genetics, researchers from the lab of Rice biochemist and cancer researcher Natasha Kirienko describe how a B12-deficient diet harms C. elegans‘ health at a cellular level, reducing the worms’ ability to metabolize branched-chain amino acids (BCAA). The research showed that the reduced ability to break down BCAAs led to a toxic buildup of partially metabolized BCAA byproducts that damaged mitochondrial health.

Researchers studied the health of two populations of worms, one with a diet sufficient in B12 and another that got too little B12 from its diet. Like the second population of worms, at least 10 percent of U.S. adults get too little B12 in their diet, a risk that increases with age.

“We used C. elegans to study the effect of diet on a host and found that one kind of food was able to dramatically increase resistance to multiple stressors — like heat and free radicals — as well as to pathogens,” said Kirienko, assistant professor of biosciences and a CPRIT Scholar in Cancer Research at Rice.

The lead scientist and co-author of the study, Kirienko said the B12 finding came as a surprise to her team, which first noticed the effect in experiments designed to investigate the mechanisms of pathogenesis of Pseudomonas aeruginosa (P. aeruginosa), a potentially deadly disease in both worms and humans that infects some 51,000 U.S. hospital patients each year, according to the Centers for Disease Control.

Her lab, like thousands of others worldwide, uses C. elegans as a model organism to study the effects of disease, drugs, toxins and other processes that affect humans and animals. In many C. elegans research labs worms are fed Escherichia coli (E. coli), a common human gut bacteria that is itself a model organism.

“We found that switching between E. coli strain OP50 and strain HT115 dramatically altered the worm’s stress tolerance,” Kirienko said. She said it took about two years of follow-up studies to isolate the biochemical mechanism of stress and pathogen resistance. Her research team included study lead co-author Alexey Revtovich and co-author Ryan Lee.

“The key difference between the two diets is the ability of HT115 and OP50 to acquire B12 from the environment,” said Revtovich, a research scientist. “We showed that HT115 is far more efficient at this, making about eight times as much of the protein that it needs to harvest B12 as compared to OP50.”

The researchers used numerous tests to confirm their results and rule out other possible mechanisms for the effect. They also found that C. elegans on an HT115 diet had the ability to resist infection by another deadly human pathogen, Enterococcus faecalis.

Lee, a Rice undergraduate student, said the study highlights the need for C. elegans labs worldwide to pay attention to the possible differential impacts of diet on experimental outcomes.

“Some labs use OP50 as their standard food, and others use HT115 or even another strain of E. coli,” Lee said. “Our results show there are significant metabolic differences between these diets, and it’s likely those differences could contribute to substantial uncertainty in research outcomes.”

Kirienko joined Rice’s faculty in 2015 thanks to a recruitment grant from the Cancer Prevention and Research Institute of Texas (CPRIT), a state ballot initiative approved in 2007 to provide $3 billion to support cancer research statewide. To date, CPRIT has awarded $2.2 billion in grants to Texas researchers, institutions and organizations through its academic research, prevention and product development research programs.

“This work is related in the sense that it focuses on mitochondrial health,” Kirienko said. “In this case, we are working to improve mitochondrial health to help fight infections. For CPRIT, we’re trying to do the opposite. We want to damage mitochondria in cancer cells to kill them. So, actually, now that we know this is important, it gives us another potential target in cancer cells.”

PUBLIC RELEASE: 13-MAR-2019

Avocado seed extract shows promise as anti-inflammatory compound

PENN STATE

An extract from the seeds of avocados exhibited anti-inflammatory properties in a laboratory study, according to Penn State researchers, and it represents a potential source for novel anti-inflammatory compounds that could be developed as a functional food ingredient or pharmaceuticals.

The researchers developed the extract over the last decade as a food colorant and it is not known whether the compounds responsible for the extract’s vibrant orange color play any role in its ability to inhibit the production of pro-inflammatory mediators, noted Joshua Lambert, associate professor of food science.

To determine the anti-inflammatory properties of the avocado seed extract, the researchers used cell culture models and enzymes that are important in immune response and inflammatory diseases. A class of immune cells called macrophages were grown in petri dishes and activated with a pro-inflammatory stimuli in the presence or absence of the avocado seed extract. The researchers measured the production of important pro-inflammatory mediators and signaling pathways in the cells after treatment with the extract.

“The next step, before we can draw further conclusions about the anti-inflammatory activity of this avocado seed extract, will be to design animal model studies,” said Lambert, co-director of Penn State’s Center for Plant and Mushroom Foods for Health. “For example, we can look at a mouse model of ulcerative colitis where we formulate the avocado seed extract into the mice diet and look at whether it is able to reduce inflammation.”

Lambert believes the study lays the groundwork for more research because it provides evidence that there are bioactive compounds in avocado seeds that have anti-inflammatory activity.

“The level of activity that we see from the extract is very good,” he said. “We saw inhibitory activity at concentrations in the low microgram-per-milliliter range, which is an acceptable amount of activity to justify further studies.”

The discovery could be important because cancer, cardiovascular diseases, arthritis, colitis and many more serious conditions are associated with chronic inflammation, explained Lambert, whose research group in the College of Agricultural Sciences conducted the study. He pointed out that the findings, published recently in Advances In Food Technology and Nutritional Sciences, are especially encouraging because avocado seeds presently go to waste.

“If we can return value to avocado growers or avocado processors, that would be a benefit,” he said. “And if we can reduce the amount of this material being dumped in landfills, that would be a good thing, given the huge amount of avocados that are consumed. This is encouraging because there is a market for other high-value sources of bioactive compounds we have tested in my lab, such as cocoa and green tea – whereas avocado seeds are essentially considered to be garbage.”

Also involved in the research was Deepti Dabas, a doctoral degree student in food science, and Gregory Ziegler, professor of food science.

The researchers have filed a patent application for the use of the extract as a food color additive. In 2016, Lambert, Ziegler and two partners founded a company, Persea Naturals, to develop the extract for this application. The identification of potential beneficial biological activity, if it is borne out in subsequent studies, may add value to the extract and provide additional avenues for development.

PUBLIC RELEASE: 13-MAR-2019

Inactive ingredients in pills and capsules may cause allergic, adverse reactions

Majority of oral medications available to consumers contain ingredients that can affect sensitive individuals

BRIGHAM AND WOMEN’S HOSPITAL

Boston, MA — A new study led by a team of investigators from Brigham and Women’s Hospital and Massachusetts Institute of Technology has found that the vast majority of the most frequently prescribed medications in the U.S. contain at least one ingredient capable of causing an adverse reaction. Known as inactive ingredients, these components are added to improve the taste, shelf-life, absorption and other characteristics of a pill, but the authors found that more than 90 percent of all oral medications tested contained at least one ingredient that can cause allergic or gastrointestinal symptoms in sensitive individuals. Such ingredients include lactose, peanut oil, gluten and chemical dyes. The team’s findings are published online in Science Translational Medicine.

“When you’re a clinician, the last thing you want to do is prescribe a medication that could cause an adverse reaction or allergic reaction in a patient,” said corresponding author C. Giovanni Traverso, MB, BChir, PhD, a gastroenterologist in the Division of Gastroenterology at the Brigham and in the Department of Mechanical Engineering at MIT. “This project was inspired by a real-life incident where a patient with Celiac disease was prescribed a medication and the formulation of the pill they picked up from the pharmacy had gluten in it. We wanted to understand the problem and drill down to characterize the entire universe of inactive ingredients across thousands of drugs.”

Traverso collaborated with biochemical data scientist Daniel Reker, PhD, internal medicine resident Steven Blum, MD, the Brigham’s executive director of Pharmacy John Fanikos, MBA, RPH, and others to analyze data on the inactive ingredients found in 42,052 oral medications that contained more than 354,597 inactive ingredients. Inactive ingredients are defined as substances that are added to a pill’s formulation but are not intended or expected to have a direct biological or therapeutic effect. Although such ingredients have been tested for safety at the population level, scattered case reports have suggested that inactive ingredients may cause adverse reactions in individuals who have allergies or intolerances.

“What is really striking about this data set is its complexity,” said Reker. “There are hundreds of different versions of pills or capsules that deliver the same medication using a different combination of inactive ingredients. This highlights how convoluted the possible choices of inactive ingredients are, but also suggests that there is a largely untapped opportunity today to specifically select the most appropriate version of a medication for a patient with unusual sensitivities.”

The team found a total of 38 inactive ingredients that have been described in the literature to cause allergic symptoms after oral exposure. The authors report that 92.8 percent of the medications they analyzed contained at least one of these inactive ingredients. Specifically, they report:

  • Approximately 45 percent of medications contained lactose;
  • approximately 33 percent of medications contained a food dye;
  • while only 0.08 percent of medications contained peanut oil, for certain drugs — such as progesterone — there are few alternatives that do not contain this inactive ingredient.

The authors note that inactive ingredients can cause an adverse reaction through an allergy (a histamine-related response that can trigger hives, difficulty breathing and/or anaphylaxis) or an intolerance, in which difficulty absorbing a substance can cause gastrointestinal symptoms. It is unclear what amount of an ingredient is necessary to trigger a reaction in sensitive individuals — the content of lactose in a medication, for instance, may be too low to cause a reaction in many patients, except for those with severe lactose intolerance or those taking many medications containing lactose.

“While we call these ingredients ‘inactive,’ in many cases, they are not. While the doses may be low, we don’t know what the threshold is for individuals to react in the majority of instances,” said Traverso. “This pushes us to think about precision care and about the role for regulation and legislation when it comes to labeling medications that contain an ingredient that may cause an adverse reaction.”

PUBLIC RELEASE: 18-MAR-2019

Pure Omega-3 prescription drug markedly reduces first, repeat and total CV events

New data show 4 gram dose of icosapent ethyl may be new, cost-effective way to prevent CV complications among patients with elevated triglycerides who have heart disease or diabetes

AMERICAN COLLEGE OF CARDIOLOGY

New Orleans, LA (Mar 18, 2019) – Taking a high dose of icosapent ethyl–a pure and stable prescription form of the omega-3 fatty acid known as EPA–significantly reduces the occurrence of first, subsequent and total ischemic events, including heart attacks, strokes and related deaths, among people at high cardiovascular risk despite already being on statin therapy, according to research presented at the American College of Cardiology’s 68th Annual Scientific Session.

Compared with placebo, icosapent ethyl cut the combined rate of first and subsequent cardiovascular deaths, nonfatal heart attacks or strokes, procedures for coronary artery disease such as stenting, or hospitalizations for unstable angina (the study’s primary endpoint) by 30 percent, demonstrating the drug may be more protective than previously reported. Earlier analyses of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT), which were primarily focused on the first occurrence of a major adverse cardiovascular event, found a 25 percent reduction. This latest analysis aimed to determine the extent to which the drug reduced the total burden of (first and subsequent) cardiovascular events.

“In looking at the totality of events–not just the first ones, but subsequent ones too–we see that the drug provides even greater reductions in ischemic events. By looking only at first events, we underestimate the true underlying treatment benefit offered,” said Deepak L. Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, professor of medicine at Harvard Medical School and the study’s lead author. “From a patient’s perspective certainly, and from a physician’s point of view, icosapent ethyl’s impact on total events is what matters most.”

Bhatt said that patients with high triglycerides who also have atherosclerosis or diabetes are especially vulnerable to repeat cardiovascular complications, so finding ways to prevent subsequent events is important and potentially lifesaving. Over a median follow-up period of approximately five years, there were nearly 3,000 events; 1,606 first events and 1,303 subsequent events, which included 762 second events, 272 third events and 269 fourth or more events. For patients taking icosapent ethyl, first events were reduced by 25 percent, second events by 32 percent, third events by 31 percent and fourth or more events were cut nearly in half (48 percent). The drug also prevented 1 in 5 cardiovascular-related deaths, as previously reported.

“With this drug, we are not only preventing that first heart attack but potentially the second stroke and maybe that third fatal event,” Bhatt said. “Prevention of such subsequent cardiovascular events could improve patient outcomes and quality of life and may lower the total cost burden of medical care.”

REDUCE-IT included 8,179 patients with elevated cardiovascular risk who were already being treated with statins. Patients with well-controlled LDL-cholesterol (>40 and ?100 mg/dL) and with elevated triglycerides (135 to 499 mg/dL) and other cardiovascular risk factors were enrolled at 473 sites in 11 countries between 2011 and 2016. About 70 percent of patients in the study had established cardiovascular disease and the rest had diabetes without known cardiovascular disease but with at least one additional cardiovascular risk factor. At baseline, median triglyceride levels were 216 mg/dL and median LDL-cholesterol was 75 mg/dL.

Patients were randomized in double-blinded fashion to receive either 2 grams icosapent ethyl twice daily or a placebo and were followed for a median of 4.9 years. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization or hospitalization for chest pain related to blockages) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction or nonfatal stroke). Follow-up visits were at four months, 12 months and annually thereafter.

The primary endpoint occurred in 17.2 percent of patients taking icosapent ethyl versus 22 percent of patients taking the placebo–an absolute risk reduction of 4.8 percent. For every 1,000 patients treated for five years with icosapent ethyl vs. placebo, about 159 events could be prevented, including 12 cardiovascular-related deaths, 42 heart attacks, 14 strokes, 76 coronary revascularizations and 16 hospitalizations for unstable angina.

“That’s a striking impact not only for that individual, but also if we consider the public health implications and potentially cost-effective ways to lower risk, this could be an appealing strategy,” Bhatt said. “We were surprised by how large an effect size there is and how much of an impact the drug is having on these patients over time, especially in the context of patients who are already well treated with background therapy.”

Baseline use of antiplatelet therapy, ACE-inhibitors/ARBs, beta blockers, aspirin and statins were all very high in REDUCE-IT, which Bhatt said provides reassurance that icosapent ethyl is providing separate and incremental benefits. “These are not undertreated patients, but they are really well treated and still remain at high cardiovascular risk,” he said, adding that this drug could potentially benefit tens of millions of patients worldwide.

Researchers also reported consistent cardiovascular benefits across subgroups of patients, including across a range of triglycerides levels, such as those with baseline or achieved triglycerides above or below 150 mg/dL, which is considered the threshold for normal by current guidelines. Bhatt said this suggests there are likely additional cardioprotective effects unique to icosapent ethyl besides triglyceride-lowering, including anti-inflammatory properties, anti-thrombotic mechanisms and cell membrane stabilization. As previously reported, the drug had a good safety profile albeit with an increased incidence of atrial fibrillation and numerically more patients with serious bleeding episodes; however, Bhatt said the overall rates were low. He reported there was no increase in the risk of stroke, the most serious complication of atrial fibrillation, but rather a statistically significant 28 percent reduction with icosapent ethyl versus placebo, as well as significant reductions in heart attacks, cardiac arrest and sudden cardiac death.

Icosapent ethyl (Vascepa) is currently approved by the U.S. Food and Drug Administration (FDA) for people with triglycerides above 500 mg/dL. Bhatt said the study drug is a prescription medicine and that the results do not apply to dietary supplement formulations, which are not approved or strictly regulated by the FDA. The high dose of EPA, which in studies appears to be more cardiovascular protective than DHA, is comparable to what one would get after eating over 20 servings of fish a week but without the related saturated fat and other components of fish, he said.

PUBLIC RELEASE: 18-MAR-2019

Healthy fats improve nerve function in obese mice

Data support further investigation of diets rich in monounsaturated fats as potential treatment for common diabetes complication

SOCIETY FOR NEUROSCIENCE

Swapping dietary saturated fats for monounsaturated fats reverses nerve damage and restores nerve function in male mice, finds new preclinical research published in JNeurosci. These data support further investigation of diets rich in healthy fats as a potential treatment for the nerve damage that occurs with diabetes, known as diabetic neuropathy.

Type 2 diabetes is associated with high-fat diets characterized by large amounts of saturated fats. In contrast, monounsaturated fatty acid-rich diets have been shown to have health benefits. Professor Eva Feldman and colleagues at the University of Michigan investigated how these two types of fats affect the progression of diabetic neuropathy, the most common complication of diabetes.

The researchers found switching mice from a saturated fat-based diet to a diet rich in monounsaturated fats derived from sunflower oil restored and protected nerve function in obese mice. Studying the beneficial effects of monounsaturated fats in sensory dorsal root ganglion neurons showed the intervention helped the cells maintain normal energy production.

These results suggest that interventions targeting dietary fats may provide a new therapeutic avenue for the treatment of diabetic neuropathy.

PUBLIC RELEASE: 17-MAR-2019

Scientists identify compounds in coffee which may inhibit prostate cancer

EUROPEAN ASSOCIATION OF UROLOGY

For the first time, scientists have identified compounds found in coffee which may inhibit the growth of prostate cancer. This is a pilot study, carried out on drug-resistant cancer cells in cell culture and in a mouse model; it has not yet been tested in humans. This work is presented at the European Association of Urology congress in Barcelona, after publication in the peer-reviewed journal The Prostate* (this press release contains additional material).

Coffee is a complex mixture of compounds which has been shown to influence human health in both positive and negative ways. There is increasing evidence that drinking certain types of coffee is associated with a reduction in incidence of some cancers, including prostate cancers**. Now Japanese scientists have studied the effects of two compounds found in coffee, kahweol acetate and cafestol, on prostate cancer cells and in animals, where they were able to inhibit growth in cells which are resistant to common anti-cancer drugs such as Cabazitaxel.

The researchers initially tested six compounds, naturally found in coffee, on the proliferation of human prostate cancers cells in vitro (i.e. in a petri-dish). They found that cells treated with kahweol acetate and cafestol grew more slowly than controls. They then tested these compounds on prostate cancer cells which had been transplanted to mice (16 mice). 4 mice were controls, 4 were treated with kahweol acetate, 4 with cafestol, with the remaining mice being treated with a combination of kahweol acetate and cafestol.

Study leader, Dr Hiroaki Iwamoto (Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Japan, first author of the study) said:

“We found that kahweol acetate and cafestol inhibited the growth of the cancer cells in mice, but the combination seemed to work synergistically, leading to a significantly slower tumour growth than in untreated mice. After 11 days, the untreated tumours had grown by around 3 and a half times the original volume (342%), whereas the tumours in the mice treated with both compounds had grown by around just over one and a half (167%) times the original size.

It is important to keep these findings in perspective. This is a pilot study, so this work shows that the use of these compounds is scientifically feasible, but needs further investigation; it does not mean that the findings can yet be applied to humans. We also found the growth reduction in transplanted tumour cells, rather than in native tumour cells. What it does show is that these compounds appear to have an effect on drug resistant cells prostate cancer cells in the right circumstances, and that they too need further investigation. We are currently considering how we might test these findings in a larger sample, and then in humans.”

Kahweol acetate and cafestol are hydrocarbons, naturally found in Arabica coffee. The coffee-making process has been found to affect whether these compounds remain in coffee after brewing (as with espresso), or whether they are stripped out (as when filtered).

Professor Atsushi Mizokami (Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Japan) added:

“These are promising findings, but they should not make people change their coffee consumption. Coffee can have both positive and negative effects (for example it can increase hypertension), so we need to find out more about the mechanisms behind these findings before we can think about clinical applications. However, if we can confirm these results, we may have candidates to treat drug-resistant prostate cancer.”

In an independent comment, Professor Zoran Culig (Professor of Experimental Urology, Medical University of Innsbruck) said:

“These are interesting findings. I would expect that those initial results will motivate researchers to use more recently developed models, such as patient-derived xenografts which express the androgen receptor. Such experiments will likely provide a definitive answer as to future perspective of this kind of treatment.”

PUBLIC RELEASE: 14-MAR-2019

Green tea cuts obesity, health risks in mice

Follow-up study in people underway

OHIO STATE UNIVERSITY

COLUMBUS, Ohio – Green tea cut obesity and a number of inflammatory biomarkers linked with poor health in a new study.

Mice fed a diet of 2 percent green tea extract fared far better than those that ate a diet without it, a finding that has prompted an upcoming study of green tea’s potential benefits in people at high risk of diabetes and heart disease.

The benefits seen in the new study, published in the Journal of Nutritional Biochemistry, appear to stem from improved gut health, including more beneficial microbes in the intestines of the mice and less permeability in the intestinal wall – a condition typically called “leaky gut” in people.

“This study provides evidence that green tea encourages the growth of good gut bacteria, and that leads to a series of benefits that significantly lower the risk of obesity,” said Richard Bruno, the study’s lead author and a professor of human nutrition at The Ohio State University.

Negative changes in the gut microbiome have been previously linked to obesity, and green tea has been shown to promote healthy bacteria. The Ohio State team wanted to explore whether there was an argument for green tea preventing obesity, inflammation and other factors connected to poor metabolic health, said Bruno, who is also a member of the Ohio Agricultural Research and Development Center.

“The results of studies looking at obesity management so far have been a real mixed bag. Some seem to support green tea for weight loss, but a lot of other research has shown no effect, likely due to the complexity of the diet relative to a number of lifestyle factors. Our goal is to figure out how it prevents weight gain,” he said. “This will lead to better health recommendations.”

Green tea has a rich history in Asian countries and has been increasingly embraced in the West, in part for its potential health benefits. Catechins, anti-inflammatory polyphenols found in green tea, have been linked to anti-cancer activity and lower risk of heart and liver disease.

Bruno and his colleagues suspected that green tea might prevent obesity and protect against inflammation in the gut based on previous studies, so they devised an experiment that examined green tea’s effects in male mice fed a normal diet and a high-fat diet designed to cause obesity. (Female mice are resistant to diet-induced obesity and insulin resistance, a precursor to diabetes, so they weren’t included.)

For eight weeks, half of the animals ate a high-fat diet designed to lead to obesity and half were fed a regular diet. In each of those groups, half ate green tea extract mixed in with their food.

Then the researchers measured body and fat tissue weight, insulin resistance and other factors that included:

  • Gut permeability, or how ‘leaky’ the gut was
  • Endotoxin translocation, or the movement of a gut bacteria-derived component to the bloodstream, where it provokes inflammation and insulin resistance
  • Inflammation in the fat tissue and intestines
  • The composition of the gut microbes, which are known to contribute to a variety of health factors

The mice fed a high-fat diet supplemented with green tea gained about 20 percent less weight and had lower insulin resistance than mice fed an otherwise identical diet without tea.

Those mice also had less inflammation within fat tissue and the intestine. Furthermore, the green tea appeared to protect against the movement of endotoxin, the toxic bacterial component, out of their guts and into the bloodstream.

Plus, the researchers found evidence of stronger – less “leaky” – guts in these mice. Leaky gut is a problem in humans that contributes to widespread low-grade inflammation and has been implicated in a number of health problems.

The researchers also found that the green tea appeared to contribute to a healthier microbial community in the guts of the mice fed a high-fat diet. Mice fed the normal, or low-fat, diet supplemented with green tea also had benefits including reduced weight gain and lower endotoxin levels and markers of leaky gut, but these were relatively modest compared with the effects seen in mice fed the high-fat diet.

Green tea consumption in the experiment would be equivalent to about 10 cups of green tea throughout the day for a person, Bruno said.

“It might seem like a lot of tea, but it’s not highly unusual in certain parts of the world,” he said.

Bruno is currently working on a human study that will explore the effects of green tea on leaky gut in people with metabolic syndrome – a condition that predisposes people to Type 2 diabetes and heart disease.

For now, he said, it’s too soon to extrapolate the findings in animals to people. He also cautioned that – should the benefits prove true in humans – green tea supplements would not be an obvious substitute for drinking the beverage over the course of a day, because of how the body metabolizes the catechins in the tea.

“Consuming a little throughout the course of a day with food – like the mice did in this study – might be better,” Bruno said.

He said he’s hopeful that future research will determine whether drinking green tea might be a good strategy for those looking to reduce their chances of becoming obese.

“Two-thirds of American adults are overweight or obese, and we know that just telling people to eat less and exercise more isn’t working. It’s important to establish complementary health-promoting approaches that can prevent obesity and related problems,” Bruno said.

PUBLIC RELEASE: 19-MAR-2019

Fountain of youth for heart health may lie in the gut

Age-related changes to microbiome fuel vascular decline, new study shows

UNIVERSITY OF COLORADO AT BOULDER

Why do blood vessels naturally stiffen and degrade as we age, boosting cardiovascular disease risk? New University of Colorado Boulder research has identified a surprising new culprit–and it lives in your gut.

“This is the first study to show that changes in the gut microbiome with aging have an adverse impact on vascular health,” said lead author Vienna Brunt, a postdoctoral researcher in the Department of Integrative Physiology. “It opens up a whole new avenue of potential interventions to prevent cardiovascular disease.”

For the study, published in the Journal of Physiology, researchers gave young mice and old mice broad-spectrum antibiotics to kill off the majority of bacteria living in their gut, aka their gut microbiome. Then they assessed the health of their vascular endothelium (the inner lining of their blood vessels) and the stiffness of their large arteries.

They also measured blood levels of inflammatory compounds, tissue-damaging free-radicals, antioxidants and the blood-vessel-expanding compound nitric oxide in both groups.

After three to four weeks of the treatment, the young mice saw no change in vascular health. The old mice, however, saw vast improvements on all measures.

“When you suppressed the microbiome of the old mice, their vascular health was restored to that of young mice,” said senior author and professor Doug Seals, director of the Integrative Physiology of Aging Laboratory. “This suggests there is something about those microorganisms that is causing vascular dysfunction.”

To assess what that something may be, the researchers then took fecal samples from another set of mice and had them genetically sequenced, comparing the gut bacteria living in the old mice with that in the young.

“In general, in the old mice, we saw an increased prevalence of microbes that are pro-inflammatory and have been previously associated with diseases,” Brunt said.

For instance, the old mice hosted significantly more Proteobacteria, a phyla that includes Salmonella and other pathogens, and pro-inflammatory Desulfovibrio.

To drill down further, the researchers measured blood levels of metabolites–small molecules produced by the gut microorganisms and absorbed into the bloodstream–in old and young mice.

Old mice had three times as much TMAO (trimethylamine N-oxide), a metabolite shown in previous studies to be linked to increased risk of atherosclerosis, heart attack and stroke.

As early as 45, risk of cardiovascular disease begins to creep up, according to the American Heart Association. By age 60-79, 70 percent of people in the United States have it. After age 80, fewer than one in five are free of it.

But just what causes healthy arteries to stiffen and lose function with age has remained somewhat of a medical mystery.

“We have long known that oxidative stress and inflammation are involved in making arteries unhealthy over time, but we didn’t know why arteries begin to get inflamed and stressed. Something is triggering this,” Seals said. “We now suspect that, with age, the gut microbiota begins producing toxic molecules, including TMAO, which get into the blood stream, cause inflammation and oxidative stress and damage tissue.”

Seals and Brunt stress that they are absolutely not suggesting people use antibiotics as a cardiovascular fountain of youth.

“We purely used antibiotics as an experimental tool. There are far too many side-effects and other problems with using it broadly,” Brunt said.

But they do believe that diets high in probiotic-rich cultured food (yogurt, kefir, kimchi) and prebiotic fiber could play a role in preventing heart disease by promoting a healthy gut microbiome.

They’re also studying a compound called dimethyl butanol, found in some olive oils, vinegars and red wines, which blocks the bacterial enzyme required to produce TMAO. Ultimately, it could be developed into a dietary supplement.

Bigger picture, the paper–along with studies linking an aging microbiome to gastrointestinal, immune and brain aging–offers one more reason to keep our resident bacteria healthy, notes an editorial accompanying the journal article.

As its authors put it:

“The fountain of youth may actually lie in the gut.”

PUBLIC RELEASE: 20-MAR-2019

Active substance from plant slows down aggressive eye cancer

Researchers at the Universities of Magdeburg and Bonn are testing a substance from the leaves of the coralberry

UNIVERSITY OF BONN

 

An active substance that has been known for 30 years could unexpectedly turn into a ray of hope against eye tumors. This is shown by a study conducted by researchers from the Universities of Bonn and Magdeburg together with US colleagues. The results are published in the renowned journal “Science Signaling“. The plant leaves of which contain the tested substance is anything but rare: At Christmas time you can find it in every well-assorted garden center.

The coralberry decorates many German living rooms during the winter months. At this time it forms bright red fruits, which make it a popular ornamental plant. The plant, originally from Korea, is surprisingly resistant to insect attack: Its leaves contain bacteria that produce a natural insecticide – a toxin with the cryptic name FR900359, abbreviated FR.

This toxin could soon become a star in a completely different field: as a potential drug against uveal melanoma, the most common and aggressive variant of eye cancer. FR has been the focus of pharmaceutical research for some time now: “The substance inhibits an important group of molecules in the cells, the Gq proteins,” explains Prof. Dr. Evi Kostenis from the Institute of Pharmaceutical Biology at the University of Bonn.

Gq proteins have a similar function in the cell as a city’s emergency control center: When the control center receives a call, it informs the police, ambulance and fire brigade as required. Gq proteins, on the other hand, can be activated by certain control signals. In their activated form, they switch different metabolic pathways on or off. However, the cell should not permanently change its behavior. The Gq proteins therefore inactivate themselves after a short time.

In uveal melanoma, however, a tiny mutation prevents two important Gq proteins from returning to their inactive state. They thus remain permanently active – this is as if the control center were constantly sending emergency vehicles to the source of the fire, even though the fire has been extinguished for days. Due to this malfunction, cells harboring this mutation begin to divide uncontrollably.

“FR can stop this division activity,” says Kostenis. “That’s something no one would have expected.” It has been known for some time that FR can prevent the activation of Gq proteins. The substance “clings” to the proteins and ensures that they remain in their inactive form. Common understanding was that FR ignores any Gq proteins that have already been activated. “Therefore, it seemed impossible for the substance to be effective in mutated and thus permanently active Gq proteins,” emphasizes Dr. Evelyn Gaffal.

A firm grip on the cancer causing protein

Gaffal recently moved from Bonn to the University of Magdeburg. Her research there includes strategies for combating skin cancer. “We also used FR in our experiments and were surprised to find that it suppresses the proliferation of cancer cells,” she explains. Scientists now also know why this is so: The mutated Gq proteins also seem to occasionally revert into their inactive form. As soon as this happens, FR900359 intervenes and gets a firm grip on the molecule. As a result, over time, more and more Gq proteins are successively withdrawn from their activated state for good.

FR has already proven its effectiveness in cell cultures and in experiments with mice suffering from cancer. But there are still a few hurdles to overcome before application in humans becomes feasible. Above all, the substance must reach the tumor cells precisely, without hitting other tissues. “Gq proteins assume vital functions practically everywhere in the body,” explains Prof. Kostenis. “If we want FR to kill only the tumor cells, we have to get the drug right there. However, this is a challenge that many other chemotherapies also have to deal with.”

FR was isolated for the first time 30 years ago by Japanese researchers. Another 25 years would pass before its biological mode of action was described – by none other than the research groups led by Professor Gabriele M. König and Professor Evi Kostenis at the Institute of Pharmaceutical Biology of the University of Bonn. This work now forms the basis for a research group of the German Research Foundation (DFG) on the group of G proteins and the possibility of their pharmacological manipulation.

PUBLIC RELEASE: 21-MAR-2019

New research shows people with PAD could have an omega-3 deficiency

New research shows that people who have PAD also have a low Omega-3 Index

WRIGHT ON MARKETING & COMMUNICATIONS

New research published in the March 18th edition of Lipids showed that people who have peripheral artery disease (PAD) have a lower Omega-3 Index compared to those who don’t have the disease.

PAD is a disease that affects the blood vessels outside the heart and brain. Evidence from other studies suggests that omega-3s affect many steps of the atherosclerotic process. More specifically, they improve endothelial function; promote vasodilatation through relaxation of smooth muscle cells; exert antioxidant, anti-inflammatory, and antithrombotic actions; delay development of plaques and increase their stability; and decrease wall stiffening.

Because PAD is essentially atherosclerosis of the leg arteries, researchers in this study believe that patients with PAD may have an omega-3 fatty acid deficiency.

To study the relationship between the Omega-3 Index and PAD, the investigators compared the Omega-3 Index in 145 patients with PAD to 34 controls without PAD.

They found that the Omega-3 Index was significantly lower in the PAD patients than the controls (5% vs 6%). When they controlled for other patient characteristics that might have influenced these findings (like age, smoking, blood pressure, diabetes, drugs, etc.), the Omega-3 Index was still lower in the cases vs. the controls.

In the final analysis, for every 1% unit reduction in the Omega-3 Index, the odds of being a PAD patient increased by 39%, and for every additional pack-year of smoking the odds of being a PAD case increased by 4%.

“It is likely that the lower inflammatory burden associated with a higher Omega-3 Index may be part of the explanation for these results,” said Bill Harris, Ph.D., one of the study’s authors. “Whether long-term use of omega-3 supplements and/or increased consumption of oily fish could prevent the development of PAD should be examined in future studies.”

 

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