261 APCNO REPORT 22 FEB 2019
APCNO REPORT FOR STAFF TESTING
By Ralph Turchiano
In this Issue:
- Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
- B-group vitamins can improve concentration among people with first episode psychosis
- Tap or bottled? Water composition impacts health benefits of tea
- Frequent use of aspirin can lead to increased bleeding
- Supplement makes (mouse) moms’ milk better; pups benefit for life
- Zinc deficiency may play a role in high blood pressure
- Vitamin D could lower the risk of developing diabetes
- Athletes can rest easy: Extreme exercise does not raise heart disease risk or mortality
- Diet drinks may be associated with strokes among post-menopausal women
- The ‘blue’ in blueberries can help lower blood pressure
- Potential link between vitamin D deficiency and loss of brain plasticity
- Lupus strongly linked to imbalances in gut microbiome
- Mouse study reveals how chronic stress promotes cancer, identifies vitamin C as therapy
- Could saffron be as effective as stimulant medicines in treating ADHD?
- Native California medicinal plant may hold promise for treating Alzheimer’s
- Vigorous exercise, fasting, hormones improve elimination of toxic, misfolded, unnecessary proteins in mouse and human cells
PUBLIC RELEASE: 9-JAN-2019
Metabolite produced by gut microbiota from pomegranates reduces inflammatory bowel disease
Urolithin A and its synthetic reduce inflammation and improve gut barrier
UNIVERSITY OF LOUISVILLE
LOUISVILLE, Ky. – Scientists at the University of Louisville have shown that a microbial metabolite, Urolithin A, derived from a compound found in berries and pomegranates, can reduce and protect against inflammatory bowel disease (IBD). Millions of people worldwide suffer from IBD in the form of either ulcerative colitis or Crohn’s disease, and few effective long-term treatments are available.
The researchers at UofL have determined that Urolithin A (UroA) and its synthetic counterpart, UAS03, mitigate IBD by increasing proteins that tighten epithelial cell junctions in the gut and reducing gut inflammation in animal models. Tight junctions in the gut barrier prevent inappropriate microorganisms and toxins from leaking out, causing inflammation characteristic of IBD. Preclinical research published today in Nature Communications shows the mechanism by which UroA and UAS03 not only reduce inflammation and restore gut barrier integrity, but also protect against colitis.
“The general belief thus far in the field is that urolithins exert beneficial effects through their anti-inflammatory, anti-oxidative properties. We have for the first time discovered that their mode of function also includes repairing the gut barrier dysfunction and maintaining barrier integrity,” said Rajbir Singh, Ph.D., a postdoctoral fellow at UofL and the paper’s first author.
Venkatakrishna Rao Jala, Ph.D., assistant professor of microbiology and immunology at UofL, led the research, conducted by Singh and other collaborators at UofL, the Institute for Stem Cell Biology and Regenerative Medicine (inStem) in Bangalore, India, the University of Toledo College of Medicine and Life Sciences, and Dalhousie University in Nova Scotia. Jala, Singh and other researchers at UofL have been investigating how metabolites produced by the human microbiota – bacteria, viruses and fungi that inhabit the human body – affect many areas of health. By understanding the effects of specific metabolites, they hope to use them directly as therapeutic agents in treating disease.
It has been reported that the microbe Bifidobacterium pseudocatenulatum INIA P815 strain in the gut has the ability to generate UroA from ellagic acid (EA), a compound found in berries and pomegranates. Variations in UroA levels, despite consumption of foods containing EA, may be the result of varied populations of bacteria responsible for the production of UroA from one individual to another, and some individuals may not have the bacteria at all.
While encouraging natural levels of UroA in the gut by consuming the appropriate foods and protecting populations of beneficial bacteria should have positive health effects, the researchers believe the use of the more stable synthetic UAS03 may prove to be therapeutically effective in cases of acute colitis. Further experiments and clinical testing are needed to test these beliefs.
“Microbes in our gut have evolved to generate beneficial microbial metabolites in the vicinity of the gut barrier,” Jala said. “However, this requires that we protect and harbor the appropriate gut microbiota and consume a healthy diet. This study shows that direct consumption of UroA or its analog can compensate for a lack of the specific bacteria responsible for production of UroA and continuous consumption of pomegranates and berries.”
Haribabu Bodduluri, Ph.D., professor of microbiology and immunology at UofL and an author of the article, said another key finding of the research is that UroA and UAS03 show both therapeutic and protective effects. Administration of UroA/UAS03 after the development of colitis reverses the condition and administration prior to development of colitis prevents it from occurring.
PUBLIC RELEASE: 14-JAN-2019
B-group vitamins can improve concentration among people with first episode psychosis
B-group vitamins can improve concentration among people experiencing first episode psychosis B-group vitamins may be beneficial for maintaining concentration skills among people experiencing a first episode of psychosis, a study by researchers from Orygen
ORYGEN, THE NATIONAL CENTRE OF EXCELLENCE IN YOUTH MENTAL HEALTH
B-group vitamins may be beneficial for maintaining concentration skills among people experiencing a first episode of psychosis, a study by researchers from Orygen, the National Centre of Excellence in Youth Mental Health, has found.
The study, led by Dr Colin O’Donnell, now at Letterkenny University Hospital, and Dr Kelly Allott from Orygen, explored the impact of increasing a person’s intake of vitamins B12, B6, and folic acid [vitamin B9] after studies in people with schizophrenia revealed that increased intake of these vitamins could decrease patients’ levels of an amino acid called homocysteine and improve their symptoms.
Dr Allott said elevated levels of homocysteine in people living with schizophrenia had been associated with more severe symptoms. “Given previous studies have shown that increasing the intake of vitamin B12, B6, and folic acid decreases homocysteine levels and improves symptoms among people with schizophrenia, we wanted to find out whether giving these vitamins to people experiencing first episode psychosis would achieve similar results,” she said.
A first episode of psychosis can be a precursor to developing schizophrenia but psychotic symptoms may also be associated with bipolar disorder or severe depression.
In the study 100 young people attending Orygen Youth Health’s Early Psychosis Prevention and Intervention Centre (EPPIC) were randomly assigned to receive either B-vitamin supplements or a placebo tablet once per day over 12 weeks. During this period, patients’ homocysteine levels, symptoms and cognitive functioning (e.g., memory, attention, language, and learning abilities) were assessed.
The results have been published in the current issue of the journal Biological Psychiatry.
Dr Allott said the results showed that participants who received the B-vitamin supplements performed better in completing concentration and attention tasks over the 12 weeks than the participants who received placebo.
“This indicates the B-vitamins could have a neuroprotective effect; although they are not improving a patient’s concentration skills, they may be protecting these skills from declining,” Dr Allott said.
“Psychosis is a diverse condition where everybody presents with different symptoms and a different biological profile. What was particularly interesting was that the participants who had abnormally high homocysteine levels at baseline were most responsive to the B-vitamin supplements, in terms of improvement in attention. The results of this study support a more personalised approach to vitamin supplementation in first episode psychosis, suggesting those with elevated homocysteine are likely to benefit most.”
PUBLIC RELEASE: 14-JAN-2019
Tap or bottled? Water composition impacts health benefits of tea
ITHACA, N.Y. – Here’s to sipping a cupful of health: Green tea steeped in bottled water has a more bitter taste, but it has more antioxidants than tea brewed using tap water, according to new Cornell University food science research published in Nutrients.
In tests conducted at Cornell’s Sensory Evaluation Center, consumers liked green tea brewed using tap water more than using bottled water, because it produced a sweeter taste. “But, when steeped in bottled water, the green tea contained about double the amount of the antioxidant epigallocatechin gallate (EGCG) – which makes it more bitter than tea brewed with tap water,” said Robin Dando, Cornell associate professor of food science.
“If you’re drinking green tea for its health properties, you should be using bottled water,” Dando said. “If you’re drinking tea for taste, tap water is better.”
A panel of more than 100 consumers could not taste the difference between black tea brewed with either tap or bottled water.
“The average consumer for black tea isn’t able to tell the difference. Whether it was tap water or bottled water, the taste differences are too subtle,” said graduate student Melanie Franks, the study’s lead author. Franks is a tea specialist who once taught chefs at the International Culinary Institute (formerly known as the French Culinary Institute, founded by the late Julia Child).
Dando believes the normal, everyday minerals in tap water – such as calcium, iron, magnesium, sodium and copper – are the products that result in lower levels of EGCG in green tea.
“Bottled water – where calcium or magnesium have been filtered out and where the iron concentration is brought down a notch – is able to extract the EGCG more efficiently,” said Dando. “With purer water, you get more health benefits out of the tea.”
PUBLIC RELEASE: 22-JAN-2019
Frequent use of aspirin can lead to increased bleeding
KING’S COLLEGE LONDON
A new study published today in the Journal of the American Medical Association (JAMA) has found that taking aspirin on a regular basis to prevent heart attacks and strokes, can lead to an increase risk of almost 50% in major bleeding episodes.
The systematic review from scientists at King’s College London and King’s College Hospital looked at the overall effects on patients who did not have known cardiovascular disease. They found that while it was associated with a lower risk of heart attacks and other cardiovascular events, it did lead to an increased risk of major bleeding.
While aspirin is known to reduce risks for those who have previously suffered strokes and heart attacks, the evidence of the role of aspirin in the initial prevention of cardiovascular events, is uncertain.
This study looked at the outcomes of trials enrolling more than 1,000 participants with no known history of cardiovascular diseases and which included a follow-up after twelve months. Participants included ones who took aspirin and other who took a placebo or had no treatment at all.
The results showed that:
- Aspirin use was associated with an 11% lower risk of cardiovascular events.
- Approximately 250 patients needed to be treated with aspirin for 5 years to prevent a single heart attack, stroke or cardiovascular death.
- Aspirin use was associated with a 43% of major bleeding events, compared to those who did not take it.
- Approximately one in 200 people treated with aspirin would have a major bleed.
- No effect was seen with aspirin on new cancer diagnoses or deaths.
Lead author, Dr Sean Zheng, Academic Clinical Fellow in Cardiology at King’s College London said: “This study demonstrates that there is insufficient evidence to recommend routine aspirin use in the prevention of heart attacks, strokes and cardiovascular deaths in people without cardiovascular disease.
“There has been more uncertainty surrounding what should be done in patients who are at higher risk of cardiovascular disease and in patients with diabetes. This study shows that while cardiovascular events may be reduced in these patients, these benefits are matched by an increased risk of major bleeding events.
“Aspirin use requires discussion between the patient and their physician, with the knowledge that any small potential cardiovascular benefits are weighed up against the real risk of severe bleeding.”
PUBLIC RELEASE: 22-JAN-2019
Supplement makes (mouse) moms’ milk better; pups benefit for life
Offspring of mothers fed nicotinamide riboside gain lasting physical and behavioral advantages
UNIVERSITY OF IOWA HEALTH CARE
Giving mouse moms a supplement called nicotinamide riboside (NR) while they are nursing provides physical and behavioral benefits to both mothers and pups, according to a new study by researchers at the University of Iowa.
Mother mice given the NR supplement lost weight faster and produced more milk than mothers not fed NR. In addition to increasing the quantity of milk the moms produced, NR supplementation also increased the quality of the milk, which contained higher levels of a protein factor that promotes brain development.
The advantages to the pups being nursed by NR-supplemented moms were striking and long-lasting. The pups were bigger and had better metabolic health than pups nursed by non-supplemented moms. As adults, they also had better motor coordination, better learning and memory, and were less anxious and more resilient to stress. Despite the fact that all the pups were treated the same after weaning and were never given NR, the offspring of the moms that received NR continued to outperform the control mice in terms of physical health, brain development, and behavior though adulthood.
The findings, published Jan. 22 in Cell Reports, suggest that NR has the potential to improve the quantity and quality of mothers’ milk in ways that could improve childhood development in a lasting fashion.
“Improving the mom’s micronutrition with NR supplementation increased the quantity and quality of her milk, and the effects on the offspring were apparent from the day the mouse pups opened their eyes and started to move around,” says lead study author Charles Brenner, PhD, UI professor and head of biochemistry at the University of Iowa Carver College of Medicine. “Now we want to know if NR can safely increase lactation in women and if taking NR increases the levels of bioactive factors in human milk like it does in mice and rats.”
NR is a form of vitamin B3 that Brenner discovered in 2004. Studies in animals and humans have shown that NR supplementation safely boosts levels of a vital cellular metabolite called NAD. Boosting NAD levels in animal models of metabolic stress produces a host of health benefits, including resistance to weight gain, improved control of blood sugar and fatty liver, reduced nerve damage, protection against heart failure, and longer lifespan.
The postpartum period, after giving birth, is a time of major, rapid metabolic change and stress for mothers that is very understudied, according to Brenner. Using lab mice, the researchers investigated what happens to mothers’ NAD levels during postpartum and examined the effects of feeding mother mice the NR supplement.
They found that during postpartum there is a dramatic diversion of NAD metabolites from the liver to the mammary glands. Levels in the liver are cut almost in half and levels of NAD metabolites increase more than 20-fold in the mammary tissue. This shift plays a crucial role in promoting milk production.
NR-supplementation in mice returned liver levels of NAD back to or above normal, and supercharged lactation, so that NR-fed moms produced more milk and the milk contained higher levels of a growth factor called brain-derived neurotrophic factor (BDNF) that enhances brain development. The NR-fed moms also lost weight faster than non-supplemented mothers.
“NR supplementation starts an amazing cascade where the resources that are supposed to flow from the liver to the mammary and into the milk are all ramped up. In addition, BDNF and likely many other bioactive factors in the milk are also increased,” says Brenner, who also is a member of the Iowa Neuroscience Institute.
The differences in the pups fed by NR-supplemented moms were also pronounced. The babies were more active and more adventurous, and they grew bigger faster than babies from non-supplemented moms. Importantly, the growth was healthy. Previous work had shown that simply increasing the amount of milk rodent pups receive increases growth, but the animals are not metabolically healthy. In contrast, the UI study found that pups nursed by the NR-fed moms have long-lasting physical and neurological advantages.
The researchers also found that the behavioral advantages seen in mice reared by NR-supplemented moms are accompanied by measurable brain changes. In young mice, offspring of NR-fed moms had higher levels of BDNF in their brains and advanced brain development, and adult offspring had higher levels of neurogenesis (production of new brain cells) compared to offspring of moms that did not receive NR.
“We are really excited to test whether NR will improve lactation in women and whether it will have some of these exciting secondary outcomes, like increasing maternal weight loss and potentially improving childhood development,” Brenner says.
PUBLIC RELEASE: 24-JAN-2019
Zinc deficiency may play a role in high blood pressure
Link found between zinc, blood pressure and kidney sodium transporter in mouse study
AMERICAN PHYSIOLOGICAL SOCIETY
Rockville, Md. (January 24, 2019)–Lower-than-normal zinc levels may contribute to high blood pressure (hypertension) by altering the way the kidneys handle sodium. The study is published ahead of print in the American Journal of Physiology–Renal Physiology.
Zinc deficiency is common in people with chronic illnesses such as type 2 diabetes and chronic kidney disease. People with low zinc levels are also at a higher risk for hypertension. The way in which the kidneys either excrete sodium into the urine or reabsorb it into the body–specifically through a pathway called the sodium chloride cotransporter (NCC)–also plays a role in blood pressure control. Less sodium in the urine typically corresponds with higher blood pressure. Recent research has suggested that zinc may help regulate proteins that in turn regulate the NCC, but a direct link between zinc-deficiency-induced hypertension has not been examined.
Researchers compared male mice with zinc deficiency to healthy controls with normal zinc levels. The zinc-deficient mice developed high blood pressure and a corresponding decrease in urinary sodium excretion. The control group did not experience the same changes. A small group of the zinc-deficient mice were fed a zinc-rich diet partway through the study. Once the animals’ zinc reached adequate levels, blood pressure began to drop and urinary sodium levels increased. “These significant findings demonstrate that enhanced renal [sodium] reabsorption plays a critical role in [zinc-deficiency]-induced hypertension,” the research team wrote.
“Understanding the specific mechanisms by which [zinc deficiency] contributes to [blood pressure] dysregulation may have an important effect on the treatment of hypertension in chronic disease settings,” the researchers added.
PUBLIC RELEASE: 30-JAN-2019
Vitamin D could lower the risk of developing diabetes
Study demonstrates role of vitamin D in controlling glycemia
THE NORTH AMERICAN MENOPAUSE SOCIETY (NAMS)
CLEVELAND, Ohio (January 30, 2019)–The benefits of vitamin D in promoting bone health are already well known. A new study out of Brazil suggests that vitamin D also may promote greater insulin sensitivity, thus lowering glucose levels and the risk of developing type 2 diabetes. Results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
Other recent studies have shown a clear relationship between vitamin D and glycemic control, suggesting that vitamin D increases insulin sensitivity and improves pancreatic beta-cell function. In this cross-sectional study involving 680 Brazilian women aged 35 to 74 years, the goal was to evaluate the possible association between vitamin D deficiency and increased glycemia.
Of the women interviewed, 24 (3.5%) reported using vitamin D supplements. Vitamin D supplementation was found to be negatively associated with high glucose levels. Habitual exposure to the sun also provided the same association, demonstrating that vitamin D deficiencies are associated with high blood glucose levels.
Study results appear in the article “Higher serum levels of vitamin D are associated with lower blood glucose levels.”
“Although a causal relationship has not been proven, low levels of vitamin D may play a significant role in type 2 diabetes mellitus,” says Dr. JoAnn Pinkerton, NAMS executive director. “Vitamin D supplementation may help improve blood sugar control, but intervention studies are still needed.”
For more information about menopause and healthy aging, visit http://www.menopause.org.
Founded in 1989, The North American Menopause Society (NAMS) is North America’s leading nonprofit organization dedicated to promoting the health and quality of life of all women during midlife and beyond through an understanding of menopause and healthy aging. Its multidisciplinary membership of 2,000 leaders in the field–including clinical and basic science experts from medicine, nursing, sociology, psychology, nutrition, anthropology, epidemiology, pharmacy, and education–makes NAMS uniquely qualified to serve as the definitive resource for health professionals and the public for accurate, unbiased information about menopause and healthy aging. To learn more about NAMS, visit http://www.menopause.org.
Public Release: 30-Jan-2019
Athletes can rest easy: Extreme exercise does not raise heart disease risk or mortality
DALLAS – Jan. 30, 2019 – Exercise is often cited as the best preventive medicine, but how much is too much for the hearts of middle-aged athletes?
Watch video: Running to extremes: High-endurance exercise OK for heart health
Sports cardiologist Dr. Benjamin Levine led a study, now published in JAMA Cardiology, to find the answer. Dr. Levine is a Professor of Internal Medicine and Director of the Institute for Exercise and Environmental Medicine, a collaboration between UT Southwestern Medical Center and Texas Health Presbyterian Hospital Dallas.
What is coronary calcium scanning and why is it important?
Coronary calcium scanning is an imaging test that helps physicians classify patients without cardiac symptoms as low, intermediate, or high risk for heart attack. It represents how much calcium (and thus cholesterol deposits) has accumulated in the blood vessels that supply the heart. The scan can help physicians determine the need for medication, lifestyle modification, and other risk-reducing measures. Learn more
“The question has never been whether exercise is good for you, but whether extreme exercise is bad for you. For the past decade or so, there’s been increasing concern that high-volume, high-intensity exercise could injure the heart. We found that high volumes of exercise are safe, even when coronary calcium levels are high,” Dr. Levine said.
High-volume, high-intensity exercise was defined in this study as at least five to six hours per week at a pace of 10 minutes per mile. The average amount of high-intensity exercise in this group was eight hours per week.
Coronary calcium is a footprint of atherosclerosis, a disease in which plaque builds up in the arteries and gives rise to heart attack and stroke. When coronary calcium is detected in the heart, the clogging process within the blood vessels has begun. The majority of high-intensity athletes had low levels of coronary calcium, though their odds of having higher levels were 11 percent greater than men who exercised less. Most importantly, the researchers found that higher calcium scores did not raise the high-intensity athletes’ risk for cardiovascular or all-cause mortality.
Dr. Levine studied data from the Cooper Center Longitudinal Study. A total of 21,758 generally healthy men ages 40 to 80 and without cardiovascular disease were followed for mortality between 1998 and 2013. The athletes, a majority of them in middle age, reported their physical activity levels and underwent coronary calcium scanning. Most were predominantly runners, but some were cyclists, swimmers, or rowers. A subgroup of athletes trained in three of these sports.
Women were not included in the study as their mortality rates are lower than for men.
Despite the findings that extreme exercise does not raise heart disease risk, Dr. Levine advises against using the protective effect of exercise to excuse poor lifestyle habits. “You cannot overcome a lifetime of bad behaviors – smoking, high cholesterol, hypertension – just from doing high levels of physical activity, so don’t use that as a magical cure,” said Dr. Levine, who holds the Distinguished Professorship in Exercise Sciences at UT Southwestern.
He also recommends caution when starting a new training program. “If you want to train for a marathon, you have to have a long-range plan to build up slowly before you achieve those volumes and intensity of exercise.”
“The known benefits of regular physical activity in the general population include decreased mortality, heart disease, diabetes, and many other medical conditions which reminds us how important it is participate in regular physical activity as recommended by the 2018 Physical Activity Guidelines,” said Dr. Laura DeFina, Chief Scientific Officer of The Cooper Institute and co-author of the study. “The current study shows no increased risk of mortality in high-volume exercisers who have coronary artery calcium. Certainly, these high-volume exercisers should review their cardiovascular disease risk with their primary care doctor or cardiologists and the study results provide helpful clinical guidance.”
“The most important take-home message for the exercising public is that high volumes of exercise are safe. The benefits of exercise far outweigh the minor risk of having a little more coronary calcium,” Dr. Levine said.
`PUBLIC RELEASE: 14-FEB-2019
Diet drinks may be associated with strokes among post-menopausal women
Stroke Journal Report
AMERICAN HEART ASSOCIATION
DALLAS, Feb. 14, 2019 — Among post-menopausal women, drinking multiple diet drinks daily was associated with an increase in the risk of having a stroke caused by a blocked artery, especially small arteries, according to research published in Stroke, a journal of the American Heart Association.
This is one of the first studies to look at the association between drinking artificially sweetened beverages and the risk of specific types of stroke in a large, racially diverse group of post-menopausal women. While this study identifies an association between diet drinks and stroke, it does not prove cause and effect because it was an observational study based on self-reported information about diet drink consumption.
Compared with women who consumed diet drinks less than once a week or not at all, women who consumed two or more artificially sweetened beverages per day were:
- 23 percent more likely to have a stroke;
- 31 percent more likely to have a clot-caused (ischemic) stroke;
- 29 percent more likely to develop heart disease (fatal or non-fatal heart attack); and
- 16 percent more likely to die from any cause.
Researchers found risks were higher for certain women. Heavy intake of diet drinks, defined as two or more times daily, more than doubled stroke risk in:
- women without previous heart disease or diabetes, who were 2.44 times as likely to have a common type of stroke caused by blockage of one of the very small arteries within the brain;
- obese women without previous heart disease or diabetes, who were 2.03 times as likely to have a clot-caused stroke; and
- African-American women without previous heart disease or diabetes, who were 3.93 times as likely to have a clot-caused stroke.
“Many well-meaning people, especially those who are overweight or obese, drink low-calorie sweetened drinks to cut calories in their diet. Our research and other observational studies have shown that artificially sweetened beverages may not be harmless and high consumption is associated with a higher risk of stroke and heart disease,” said Yasmin Mossavar-Rahmani, Ph.D., lead author of the study and associate professor of clinical epidemiology and population health at the Albert Einstein College of Medicine in the Bronx, New York.
Researchers analyzed data on 81,714 postmenopausal women (age 50-79 years at the start) participating in the Women’s Health Initiative study that tracked health outcomes for an average of 11.9 years after they enrolled between 1993 and 1998. At their three-year evaluation, the women reported how often in the previous three months they had consumed diet drinks such as low calorie, artificially sweetened colas, sodas and fruit drinks. The data collected did not include information about the specific artificial sweetener the drinks contained.
The results were obtained after adjusting for various stroke risk factors such as age, high blood pressure, and smoking. These results in postmenopausal women may not be generalizable to men or younger women. The study is also limited by having only the women’s self-report of diet drink intake.
“We don’t know specifically what types of artificially sweetened beverages they were consuming, so we don’t know which artificial sweeteners may be harmful and which may be harmless,” Mossavar-Rahmani said.
The American Heart Association recently published a science advisory that found there was inadequate scientific research to conclude that low-calorie sweetened beverages do – or do not – alter risk factors for heart disease and stroke in young children, teens or adults. The Association recognizes diet drinks may help replace high calorie, sugary beverages, but recommends water (plain, carbonated and unsweetened flavored) as the best choice for a no calorie drink.
“Unfortunately, current research simply does not provide enough evidence to distinguish between the effects of different low-calorie sweeteners on heart and brain health. This study adds to the evidence that limiting use of diet beverages is the most prudent thing to do for your health,” said Rachel K. Johnson, Ph.D., R.D., professor of nutrition emeritus, University of Vermont and the chair of the writing group for the American Heart Association’s science advisory, Low-Calorie Sweetened Beverages and Cardiometabolic Health.
“The American Heart Association suggests water as the best choice for a no-calorie beverage. However, for some adults, diet drinks with low calorie sweeteners may be helpful as they transition to adopting water as their primary drink. Since long-term clinical trial data are not available on the effects of low-calorie sweetened drinks and cardiovascular health, given their lack of nutritional value, it may be prudent to limit their prolonged use” said Johnson.
Public Release: 20-Feb-2019
The ‘blue’ in blueberries can help lower blood pressure
King’s College London
A new study published in the Journal of Gerontology Series A has found that eating 200g of blueberries every day for a month can lead to an improvement in blood vessel function and a decrease in systolic blood pressure in healthy people.
Researchers from King’s College London studied 40 healthy volunteers for one month. They were randomly given either a drink containing 200g of blueberries, or a matched control drink daily.
The team monitored chemicals in volunteers’ blood and urine as well as their blood pressure and flow-mediated dilation (FMD) of the brachial artery: a measure of how the artery widens when blood flow increases, which is considered a sensitive biomarker of cardiovascular disease risk.
In a further study, researchers compared the effects of a blueberry drink with those of purified anthocyanins, a type of phytochemical responsible for the blue, red, pink and purple colour of some fruits and vegetables such as berries and red grapes. They also compared this with control drinks containing either similar levels of fibre, mineral or vitamins found in blueberries.
They found that:
- Effects on blood vessel function were seen two hours after consumption of the blueberry drinks and were sustained for one month even after an overnight fast.
- Over the course of the month, blood pressure was reduced by 5mmHg. This is similar to what is commonly seen in studies using blood pressure lowering medication.
- The drinks containing purified anthocyanins led to improvements in endothelial function. Endothelial cells act as a barrier between the blood or lymph and the surrounding body tissue, as well as playing key roles in blood clotting and regulating blood pressure.
- Neither the control drink, the control with fibre or the control with minerals and vitamins had a significant effect on FMD at two and six hours after consumption.
Lead researcher Dr Ana Rodriguez-Mateos from the Department of Nutritional Sciences at King’s College London said: “Although it is best to eat the whole blueberry to get the full benefit, our study finds that the majority of the effects can be explained by anthocyanins.
“If the changes we saw in blood vessel function after eating blueberries every day could be sustained for a person’s whole life, it could reduce their risk of developing cardiovascular disease by up to 20%.”
Public Release: 19-Feb-2019
Potential link between vitamin D deficiency and loss of brain plasticity
University of Queensland
University of Queensland research may explain why vitamin D is vital for brain health, and how deficiency leads to disorders including depression and schizophrenia.
Associate Professor Thomas Burne at UQ’s Queensland Brain Institute led the studies, which provide the groundwork for research into better prevention and treatments.
“Over a billion people worldwide are affected by vitamin D deficiency, and there is a well-established link between vitamin D deficiency and impaired cognition,” Dr Burne said.
“Unfortunately, exactly how vitamin D influences brain structure and function is not well understood, so it has remained unclear why deficiency causes problems.”
Dr Burne’s team found that vitamin D levels affect a type of ‘scaffolding’ in the brain, called perineuronal nets.
“These nets form a strong, supportive mesh around certain neurons, and in doing so they stabilise the contacts these cells make with other neurons,” he said.
Researchers removed vitamin D from the diet of a group of healthy adult mice, and after 20 weeks found a significant decline in their ability to remember and learn compared to a control group.
Dr Burne said the vitamin D deficient group had a pronounced reduction in perineuronal nets in the hippocampus, the brain region crucial to memory formation.
“There was also a stark reduction in both the number and strength of connections between neurons in that region.”
Dr Burne’s team propose that vitamin D plays an important role in keeping perineuronal nets stable, and that when vitamin D levels drop, this ‘scaffolding’ is more easily degraded by enzymes.
“As neurons in the hippocampus lose their supportive perineuronal nets, they have trouble maintaining connections, and this ultimately leads to a loss of cognitive function.”
Associate Professor Burne said the hippocampus may be most strongly affected by vitamin D deficiency because it is much more active than other brain regions.
“It’s like the canary in the coalmine–it might fail first because its high energy requirement makes it more sensitive to the depletion of essential nutrients like vitamin D.
“Intriguingly, the right side of the hippocampus was more affected by vitamin D deficiency than the left side.”
Associate Professor Burne said loss of function in this area could be an important contributor to the hallmarks of schizophrenia, including severe memory deficits and a distorted perception of reality.
“The next step is to test this new hypothesis on the link between vitamin D deficiency, perineuronal nets and cognition,” he said.
“We are also particularly excited to have discovered these nets can change in adult mice.
“I’m hoping that because they’re dynamic there is a chance that we can rebuild them, and that could set the stage for new treatments.”
The research is published in Brain Structure and Function and Trends in Neuroscience.
Public Release: 19-Feb-2019
Lupus strongly linked to imbalances in gut microbiome
NYU Langone Health / NYU School of Medicine
The disease systemic lupus erythematosus (SLE) — marked by the attack on joints, skin, and kidneys by the body’s immune system — is linked to an abnormal mix of bacteria in the gut. This is according to a new study led by scientists at NYU School of Medicine.
While bacterial imbalances have been tied to many immune-related diseases, including inflammatory bowel disease, arthritis, and some cancers, the authors of the current study say their experiments are the first detailed evidence of a link between bacterial imbalances in the gut and potentially life-threatening forms of SLE.
The new study, publishing in the Annals of Rheumatic Diseases online Feb. 19, showed that 61 women diagnosed with SLE had roughly five times more gut bacteria known as Ruminococcus gnavus, than 17 women of similar ages and racial backgrounds who did not have the disease and were healthy. Lupus is more common in women than in men.
Moreover, study results showed that disease “flares,” which can range from instances of skin rash and joint pain to severe kidney dysfunction requiring dialysis, closely tracked major increases in R. gnavus bacterial growth in the gut, alongside the presence in blood samples of immune proteins called antibodies, specifically shaped to attach to the bacteria. Study participants with kidney flares had especially high levels of antibodies to R. gnavus.
The authors say the specific causes of lupus, which affects as many as 1.5 million Americans, are unknown, although many suspect that genetic factors are partly responsible.
“Our study strongly suggests that in some patients bacterial imbalances may be driving lupus and its associated disease flares,” says study senior investigator and immunologist Gregg Silverman, MD. “Our results also point to leakages of bacteria from the gut as a possible immune system trigger of the disease, and suggest that the internal gut environment may therefore play a more critical role than genetics in renal flares of this all too often fatal disease,” says Silverman, a professor in the departments of Medicine and Pathology at NYU Langone Health. He also suspects that antibodies to R. gnavus provoke a “continuous and unrelenting” immune attack on organs involved in flares.
Among the more practical consequences of the new research, Silverman says, could be the development of relatively simple blood tests to detect antibodies to leaked bacteria, which in turn could also be used to diagnose and track lupus progression and therapy, even in the disease’s earliest stages. Current tests, he says, are often inconclusive and rely on signs and symptoms that only appear after the disease has already advanced.
Silverman, who also serves as associate director of rheumatology at NYU Langone, cautions that larger studies are needed to confirm how these bacteria may cause lupus. But if future experiments show similarly positive results, then it could result in shifts from current approaches to treating the disease, which focus on immune-suppressing anticancer medications to relieve symptoms and injury to the kidneys.
If the study team’s results are validated, then some current treatments may actually be causing harm if they impair overall immune defenses against infection.
Instead, Silverman says, future treatments could include inexpensive probiotics or dietary regimens that impede R. gnavus growth and prevent flares. Fecal transplants from healthy individuals would also be a possibility.
Alternatively, Silverman says, new treatments could also be used to promote growth of Bacteroides uniformis, bacteria thought to hinder growth of R. gnavus in the gut and whose numbers decreased by as much as fourfold in study participants with lupus when compared to those without the disease. Experts say that over a 1,000 different types of bacteria make up the human gut microbiome.
For the study, researchers analyzed blood and stool samples from participants. Researchers were surprised to find strong immune antibody reactions to R. gnavus in the blood because the gut lining prevents the bacterium from escaping to other parts of the body. Researchers say this suggests that small pieces of the bacteria, known as antigens, must have “leaked” into the gut to trigger the immune reaction.
Public Release: 18-Feb-2019
Mouse study reveals how chronic stress promotes cancer, identifies vitamin C as therapy
University of Illinois College of Agricultural, Consumer and Environmental Sciences
URBANA, Ill. – Cancer: The word alone evokes dread, anxiety, and fear. Accordingly, many women living with the disease and undergoing treatment experience chronic stress and depression. Scientists have demonstrated, in studies with rodents and humans, that stress can exacerbate cancer’s progression, but it wasn’t clear how.
A new study, published in the Journal of Clinical Investigation, establishes that the stress hormone epinephrine sets off a cascade of biochemical reactions that favor breast cancer growth and spread.
In the study, the researchers first demonstrated the effects of chronic stress on cancer stem cell growth, a novel twist on previous research that did not specifically focus on these self-perpetuating cells.
“You can kill all the cells you want in a tumor, but if the stem cells, or mother cells, are not killed, then the tumor is going to grow and metastasize. This is one of the first studies to link chronic stress specifically with the growth of breast cancer stem cells,” says Keith Kelley, emeritus professor in the Department of Animal Sciences and the College of Medicine at the University of Illinois, and an author on the study.
To do this, they induced chronic stress in mice, by placing them in small enclosures that limited their movement. All the mice were stressed for a week before being inoculated with either human or mouse breast cancer cells. After inoculation, the mice were split into two groups: controls, which were moved into large cages; and stressed, which stayed in the small enclosures for an additional 30 days.
Confirming the researchers’ expectations, the mice experiencing chronic stress showed behavioral changes consistent with anxiety and depression. They also had bigger, faster-growing tumors and more cancer stem cells than mice in control conditions.
Having demonstrated the link between chronic stress, mood changes, and enhanced growth of breast cancer stem cells, the scientists went on to investigate the underlying biochemical underpinnings that caused stress to increase growth of cancer cells.
“The direct signaling network between stress pathways and a cancer-propagating system remains almost completely unknown,” says Quentin Liu of the Institute of Cancer Stem Cell at Dalian Medical University in China and principal investigator on the study. “A better understanding of the biochemistry that causes stress to increase the growth of cancer cells could lead us toward targeted drug interventions, one of which we discovered in this work.”
Multiple lines of evidence led the scientists toward epinephrine, one of the body’s major stress hormones. First, epinephrine levels were significantly elevated in mice that experienced stress for the duration of the experiment. Second, in stressed mice that received treatments to inactivate the receptor for epinephrine – ADRB2 – tumors were significantly smaller and fewer stem cells were found.
“When most people think of stress, they think it’s cortisol that’s suppressing the immune system. The amazing thing is cortisol was actually lower after a month of stress,” Kelley says.
Once epinephrine binds to one of its two receptors, ADRB2, it elevates levels of an enzyme called lactate dehydrogenase. In normal situations, this enzyme delivers quick energy to muscles in a fight-or-flight situation and produces lactate as a byproduct. But cancer cells need lactate for energy. With excessive amounts of lactate dehydrogenase in chronically stressed individuals, cancer-causing genes are activated and cancer cells proliferate.
“These data provide a novel pathway that explains how elevated epinephrine caused by chronic stress promotes breast cancer progression by acting directly on cancer stem cells,” Liu says.
To evaluate the clinical significance of their findings with mice, the scientists measured epinephrine in the blood of 83 human breast cancer patients. Women with high levels of the stress hormone also had high levels of lactate dehydrogenase in biopsied breast cancer tissue, compared with adjacent non-cancerous tissue. Importantly, and consistent with findings in mice, patients with high serum epinephrine had significantly lower overall survival and disease-free survival compared to patients with low epinephrine levels.
In a final test, the researchers grew breast cancer cells in the lab and introduced a wide variety of FDA-approved cancer drugs. Several treatments, including vitamin C, suppressed lactate dehydrogenase production. When vitamin C was injected into stressed mice, tumors shrank.
Scientists have suspected Vitamin C’s cancer-fighting potential for decades, and several clinical trials have demonstrated positive results. This study contributes a new understanding of the vitamin’s action in biochemical pathways relevant to chronically stressed breast cancer patients.
“Taken together, these findings show that vitamin C might be a novel and effective therapeutic agent for targeting cancer in patients undergoing chronic stress,” Liu says.
Public Release: 21-Feb-2019
Could saffron be as effective as stimulant medicines in treating ADHD?
Mary Ann Liebert, Inc./Genetic Engineering News
New Rochelle, NY, February 21, 2019–A new short-term pilot study in children and teens 6-17 years old with attention-deficit hyperactivity disorder (ADHD) has shown saffron to be as effective at controlling symptoms as methylphenidate, the commonly prescribed drug Ritalin. Saffron may be a promising herbal alternative for treating ADHD, particularly for the 30% of patients who do not respond to or cannot tolerate stimulants like methylphenidate, as reported in an article published in the Journal of Child and Adolescent Psychopharmacology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article free on the Journal of Child and Adolescent Psychopharmacology website through March 21, 2019.
The article entitled “Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study” was coauthored by Sara Baziar, MD, Ali Aqamolaei, MD and colleagues from Tehran University of Medical Sciences, Iran. The researchers note that saffron also has anti-depressant and memory-enhancing properties. They compared the effects of Crocus sativus L. to methylphenidate in 54 patients over a 6-week period and showed no significant difference in effectiveness as well as similar frequency of adverse effects.
“This is a very interesting study and an intriguing finding. It is worthy of replication and further study to understand the mechanism of action,” says Harold S. Koplewicz, MD, Editor-in-Chief of the Journal of Child and Adolescent Psychopharmacology and President of the Child Mind Institute in New York.
Public Release: 20-Feb-2019
Native California medicinal plant may hold promise for treating Alzheimer’s
Salk scientists identify possible healing compound in Yerba santa
LA JOLLA–(February 20, 2019) The medicinal powers of aspirin, digitalis, and the anti-malarial artemisinin all come from plants. A Salk Institute discovery of a potent neuroprotective and anti-inflammatory chemical in a native California shrub may lead to a treatment for Alzheimer’s disease based on a compound found in nature. The research appears in the February 2019 issue of the journal Redox Biology.
“Alzheimer’s disease is a leading cause of death in the United States,” says Senior Staff Scientist Pamela Maher, a member of Salk’s Cellular Neurobiology Laboratory, run by Professor David Schubert. “And because age is a major risk factor, researchers are looking at ways to counter aging’s effects on the brain. Our identification of sterubin as a potent neuroprotective component of a native California plant called Yerba santa (Eriodictyon californicum) is a promising step in that direction.”
Native California tribes, which dubbed the plant “holy herb” in Spanish, have long used Yerba santa for its medicinal properties. Devotees brew its leaves to treat respiratory ailments, fever and headaches; and mash it into a poultice for wounds, sore muscles and rheumatism.
To identify natural compounds that might reverse neurological disease symptoms, Maher applied a screening technique used in drug discovery to a commercial library of 400 plant extracts with known pharmacological properties. The lab had previously used this approach to identify other chemicals (called flavonoids) from plants that have anti-inflammatory and neuroprotective properties.
Through the screen, the lab identified a molecule called sterubin as Yerba santa’s most active component. The researchers tested sterubin and other plant extracts for their impact on energy depletion in mouse nerve cells, as well as other age-associated neurotoxicity and survival pathways directly related to the reduced energy metabolism, accumulation of misfolded, aggregated proteins and inflammation seen in Alzheimer’s. Sterubin had a potent anti-inflammatory impact on brain cells known as microglia. It was also an effective iron remover–potentially beneficial because iron can contribute to nerve cell damage in aging and neurodegenerative diseases. Overall, the compound was effective against multiple inducers of cell death in the nerve cells, according to Maher.
“This is a compound that was known but ignored,” Maher says. “Not only did sterubin turn out to be much more active than the other flavonoids in Yerba santa in our assays, it appears as good as, if not better than, other flavonoids we have studied.”
Next, the lab plans to test sterubin in an animal model of Alzheimer’s, then determine its drug-like characteristics and toxicity levels in animals. With that data, Maher says, it might be possible to test the compound in humans, although it would be critical to use sterubin derived from plants grown under standardized, controlled conditions. She says the team will likely generate synthetic derivatives of sterubin.
Public Release: 20-Feb-2019
Vigorous exercise, fasting, hormones improve elimination of toxic, misfolded, unnecessary proteins in mouse and human cells
Harvard Medical School
The body’s ability to adapt to changing conditions and shifting physiologic demands is essential to survival. To do so, each cell must be able to dispose of damaged or unnecessary proteins–a quality-control mechanism critical for cellular performance and for the health of the entire organism.
Now, a study from Harvard Medical School shows that intense exercise, fasting and an array of hormones can activate cells’ built-in protein disposal system and enhance their ability to purge defective, toxic or unneeded proteins.
The findings, published Feb. 19 in PNAS, reveal a previously unknown mechanism used by the body to rapidly turn on the molecular machinery responsible for junk-protein removal, allowing cells to adapt their protein content to meet new demands. This mechanism, the study shows, is triggered by fluctuations in hormone levels, which signal changes in physiologic conditions.
“Our findings show that the body has a built-in mechanism for cranking up the molecular machinery responsible for waste-protein removal that is so critical for the cells’ ability to adapt to new conditions,” said Alfred Goldberg, senior author on the study and professor of cell biology in the Blavatnik Institute at Harvard Medical School.
Cellular house cleaning in disease and health
Malfunctions in the cells’ protein-disposal machinery can lead to the accumulation of misfolded proteins, which clog up the cell, interfere with its functions and, over time, precipitate the development of diseases, including neurodegenerative conditions such as ALS and Alzheimer’s.
The best-studied biochemical system used by cells to remove junk proteins is the ubiquitin-proteasome pathway. It involves the tagging of defective or unneeded proteins with ubiquitin molecules–a process known as the “kiss of death,” which marks proteins for destruction by the cell’s protein-disposal unit, known as 26S proteasome.
Past research by Goldberg’s lab has shown that this machinery can be activated by pharmacological agents that boost the levels of a molecule known as cAMP, an intracellular messenger, which in turn switches on the enzyme protein kinase A.
The team’s previous work has shown that cAMP-stimulating drugs enhance the destruction of defective or toxic proteins, particularly mutant proteins that can lead to neurodegenerative conditions.
The new findings, however, reveal that this quality-control process is continually regulated independent of drugs by shifts in physiological states and corresponding changes in hormones.
Past research, including work from Goldberg’s lab, has focused predominantly on reining in overactive protein breakdown–a state of excessive protein removal that can cause muscle wasting in cancer patients or give rise to several types of muscle atrophy. In fact, a proteasome inhibitor drug that tamps down the activity of the protein-disposal machinery, developed by Goldberg and team, has been widely used for the treatment of multiple myeloma, a common type of blood cancer, marked by abnormal protein accumulation and overworked proteasomes.
The team’s latest work, by contrast, is focused on developing therapies that do the exact opposite–invigorate the cell’s protein-disposal machinery when it is too sluggish. These newest findings open the door–at least conceptually–to precisely such treatments.
“We believe our findings set the stage for the development of therapies that harness the cells’ natural ability to dispose of proteins and thus enhance the removal of toxic proteins that cause disease,” said study lead investigator Jordan VerPlank, a postdoctoral research fellow in cell biology in the Blavatnik Institute at Harvard Medical School.
Such treatments, the team said, may not necessarily involve the design of new molecules but instead stimulate the cell’s built-in capacity for quality control.
“This is truly a new way of looking at whether we can turn up the cellular vacuum cleaner,” Goldberg said. “We thought this would require the development of new types of molecules, but we hadn’t truly appreciated that our cells continually activate this process.
“The beauty and the surprise of it is that such new treatments may involve churning a natural endogenous pathway and harnessing the body’s preexisting capacity to perform quality control,” he added.
That exercise has many salutary effects is already well known, the researchers said, but the new findings also hint at the possibility that exercise and fasting could help reduce the risk of developing conditions associated with the accumulation of misfolded proteins, such as Alzheimer’s and Parkinson’s. That possibility, however, remains to be explored in subsequent research, the team noted.
In their experiments, the researchers analyzed the effects of exercise on cells obtained from the thigh muscles of four human volunteers before and after vigorous biking. Following exercise, the proteasomes of these cells showed dramatically more molecular marks of enhanced protein degradation, including greater levels of cAMP, the chemical trigger that initiates the cascade that leads to protein degradation inside cells. The same changes were observed in the muscles of anesthetized rats whose hind legs were stimulated to contract repeatedly.
Fasting–even for brief periods–produced a similar effect on the cells’ protein-breakdown machinery. Fasting increased proteasome activity in the muscle and liver cells of mice deprived of food for 12 hours–the equivalent of an overnight fast.
In another round of experiments, the researchers exposed the liver cells of mice to glucagon–the hormone that stimulates the production of glucose as fuel for cells and tissues during periods of food deprivation or whenever blood sugar levels drop down. The researchers observed that glucagon exposure stimulated proteasome activity and enhanced the cells’ capacity to destroy misfolded proteins.
Exposure to the fight-or-flight hormone epinephrine produced a similar effect. Epinephrine, or adrenaline in common parlance, is responsible for stimulating the liver and muscle to mobilize energy reserves to boost heart rate and muscle strength during periods of physiologic stress. Liver cells treated with epinephrine showed marked increases in cAMP, as well as enhanced 26S proteasome activity and protein degradation. Epinephrine exposure also boosted proteasome activity–a marker of protein degradation–in the working hearts of rats. Similarly, when researchers exposed the kidney cells of mice to vasopressin–the antidiuretic hormone that helps the body retain water and prevents dehydration–they observed higher levels of protein degradation as well.
Taken together, these findings demonstrate that the rate of protein degradation can rise and fall swiftly in a variety of tissues in response to shifting conditions and that such changes are mediated by fluctuations in hormone levels. This response was also surprisingly rapid and short-lived, the scientists noted. For example, exposure to the antidiuretic hormone triggered protein breakdown in kidney cells within five minutes and subsided to pre-exposure levels within an hour, the experiments showed.
The findings show that a diverse set of hormones that stimulate the intracellular messenger cAMP appear to share a common mechanism that alters the composition of cells. cAMP-stimulating hormones have long been known to modify gene expression, but this latest research reveals they also play a critical role in cellular “house cleaning” by disposing of proteins that are no longer needed.
A new twist on a classic concept
Even the most mundane of activities–eating, sleeping, exercise–require the cells in our body to modulate their composition minute by minute in order to cope with new demands, all in the name of maintaining proper cellular function and averting harm. The new research reveals that some of these protective shifts occur in our cells’ protein-disposal system, where misfolded or unneeded proteins are removed promptly and new ones in demand are synthesized swiftly.
The new findings build on observations about the physiologic effects of hormones first made by Harvard Medical School physician Walter Cannon nearly a century ago and elegantly captured in his book The Wisdom of the Body (1932). Some of Cannon’s most notable work includes defining the mechanism of action of the hormone epinephrine and its role in the body’s fight-or-flight response–a key survival mechanism marked by a cascade of physiologic changes during times of high stress.
Epinephrine is one of the hormones whose action on the cells’ protein-disposal machinery is now illuminated by Goldberg’s latest work. In a twist of symbolic coincidence, Goldberg’s lab occupies the very space where Cannon made his historic observations on the same hormone a hundred years ago.
“We think ours is truly a neoclassical discovery that builds on findings and observations made right here, in this very building, nearly a century ago,” Goldberg said.