Health Articles Week of 5/11-5/17

Vitamin D deficiency appears to play role in COVID-19 mortality rates

Northwestern University, May 8, 2020

After studying global data from the novel coronavirus (COVID-19) pandemic, researchers have discovered a strong correlation between severe vitamin D deficiency and mortality rates.

Led by Northwestern University, the research team conducted a statistical analysis of data from hospitals and clinics across China, France, Germany, Italy, Iran, South Korea, Spain, Switzerland, the United Kingdom (UK) and the United States.

The researchers noted that patients from countries with high COVID-19 mortality rates, such as Italy, Spain and the UK, had lower levels of vitamin D compared to patients in countries that were not as severely affected.

This does not mean that everyone—especially those without a known deficiency—needs to start hoarding supplements, the researchers caution.

“While I think it is important for people to know that vitamin D deficiency might play a role in mortality, we don’t need to push vitamin D on everybody,” said Northwestern’s Vadim Backman, who led the research. “This needs further study, and I hope our work will stimulate interest in this area. The data also may illuminate the mechanism of mortality, which, if proven, could lead to new therapeutic targets.”

The research is available on medRxiv, a preprint server for health sciences.

Backman is the Walter Dill Scott Professor of Biomedical Engineering at Northwestern’s McCormick School of Engineering. Ali Daneshkhah, a postdoctoral research associate in Backman’s laboratory, is the paper’s first author.

Backman and his team were inspired to examine vitamin D levels after noticing unexplained differences in COVID-19 mortality rates from country to country. Some people hypothesized that differences in healthcare quality, age distributions in population, testing rates or different strains of the coronavirus might be responsible. But Backman remained skeptical.

“None of these factors appears to play a significant role,” Backman said. “The healthcare system in northern Italy is one of the best in the world. Differences in mortality exist even if one looks across the same age group. And, while the restrictions on testing do indeed vary, the disparities in mortality still exist even when we looked at countries or populations for which similar testing rates apply.

“Instead, we saw a significant correlation with vitamin D deficiency,” he said.

By analyzing publicly available patient data from around the globe, Backman and his team discovered a strong correlation between vitamin D levels and cytokine storm—a hyperinflammatory condition caused by an overactive immune system—as well as a correlation between vitamin D deficiency and mortality.

“Cytokine storm can severely damage lungs and lead to acute respiratory distress syndrome and death in patients,” Daneshkhah said. “This is what seems to kill a majority of COVID-19 patients, not the destruction of the lungs by the virus itself. It is the complications from the misdirected fire from the immune system.”

This is exactly where Backman believes vitamin D plays a major role. Not only does vitamin D enhance our innate immune systems, it also prevents our immune systems from becoming dangerously overactive. This means that having healthy levels of vitamin D could protect patients against severe complications, including death, from COVID-19.

“Our analysis shows that it might be as high as cutting the mortality rate in half,” Backman said. “It will not prevent a patient from contracting the virus, but it may reduce complications and prevent death in those who are infected.”

Backman said this correlation might help explain the many mysteries surrounding COVID-19, such as why children are less likely to die. Children do not yet have a fully developed acquired immune system, which is the immune system’s second line of defense and more likely to overreact.

“Children primarily rely on their innate immune system,” Backman said. “This may explain why their mortality rate is lower.”

Backman is careful to note that people should not take excessive doses of vitamin D, which might come with negative side effects. He said the subject needs much more research to know how vitamin D could be used most effectively to protect against COVID-19 complications.

“It is hard to say which dose is most beneficial for COVID-19,” Backman said. “However, it is clear that vitamin D deficiency is harmful, and it can be easily addressed with appropriate supplementation. This might be another key to helping protect vulnerable populations, such as African-American and elderly patients, who have a prevalence of vitamin D deficiency.”

Study finds heavy cannabis use affects human genome

University of Canterbury, May 7, 2020

Heavy cannabis use has an impact on human DNA but the effect is stronger in people who smoke tobacco as well, according to new University of Canterbury (UC) research.

The study, recently published in Translational Psychiatry, investigates how heavy cannabis use can lead to alterations in “DNA methylation”—chemical changes in the body that influence how our genes work.

UC College of Science lecturer Dr. Amy Osborne, lead author of the UC study, in collaboration with colleagues from the University of Otago Christchurch, University of Otago, and ESR, says there is already strong evidence that chronic, heavy use of cannabis can increase the risk of mental health issues such as depression and schizophrenia. It is also associated with heart disease.

“This study shows how cannabis use is linked to changes in gene pathways that may explain the link between heavy cannabis use and those adverse health outcomes,” she says. “However, in terms of the effect on the genome and DNA methylation, cannabis appears to have a distinct and somewhat more subtle effect than tobacco. It’s not altering gene pathways to the same extent, but it does affect them in very specific ways.”

The 48 subjects in the new research—all heavy cannabis users—were members of the Christchurch Health and Development longitudinal study. Blood samples were taken when they were aged 28 and analysed for DNA methylation differences between cannabis users and non-users.

The biggest changes were in those who smoked tobacco as well as cannabis, but there was also evidence of distinct and specific DNA alterations in those who smoked only cannabis, compared to non-users.

The most affected genes were identified as those involved in brain and heart function.

Dr. Osborne, who specialises in genomics, says cannabis use is an important public health issue, particularly in New Zealand where a referendum on whether the sale, use, possession and production of cannabis should be legalised is due to be held in September 2020.

“We think assessing cannabis’s potential effect on DNA is timely. It’s currently the most widely used illicit psychoactive substance in the world and this could be predicted to increase with decriminalisation or legalisation,” she says.

Unusually, the Christchurch Health and Development Study cohort contained cannabis users who had never smoked cigarettes, providing a valuable opportunity to investigate the specific effects of cannabis on DNA methylation in the human genome.

Dr. Osborne says the UC study suggests that, while tobacco has a stronger effect on DNA than cannabis, cannabis appears to exert specific effects on genes involved in brain and heart function. More research with a larger sample size is needed.

“Our data are suggestive of a role for DNA methylation in the biological response to cannabis. We also found the effects of cannabis use on our genomes differ from, and are less pronounced than, the effects of tobacco use.

“For this reason, caution should be taken when interpreting similar cannabis exposure studies that do not, or cannot, exclude cigarette smokers.”

Is vitamin K the secret key to bone strength?

Tufts University, May 8, 2020

When we think of strong bones, we usually think of milk, a rich source of the nutrients that promote bone density: calcium and vitamin D. But we may be overlooking another important nutrient created closer to home—in our own gut, to be exact.

Vitamin K produced by certain types of bacteria that colonize the gut could also bolster bones, according to scientists Kyla Shea of the Vitamin K Laboratory at the USDA’s Human Nutrition Research Center on Aging (HNRCA) at Tufts University and Chris Hernandez of Cornell University’s Sibley School of Mechanical and Aerospace Engineering.

Hernandez reached out to collaborate with the Vitamin K Laboratory, headed by HNRCA Director Sarah Booth, after seeing reduced bone strength but unchanged bone density in mice whose gut microbiomes had been modified (this research was published in 2017 in the Journal of Bone and Mineral Research). Combing through the bone strength literature to identify the nutrient that might have been lost, Hernandez found that vitamin K had often been associated with fracture risk, but not bone density.

“The HNRCA is the perfect place to research this question. Not only does it have the world’s experts on the biochemistry of vitamin K, but it also has unique facilities that make it possible to manipulate the form of the vitamin that is involved here and to monitor the process,” said Hernandez.

Most of the vitamin K in our diet comes from green vegetables, but the gut bacteria synthesize a different form of it, Shea said. It’s this form of vitamin K that could be affecting bone strength, although the exact mechanism is yet to be determined.

“Many clinical trials with vitamin K measure bone mineral density outcomes, but there may be links with bone strength independent of density,” Shea said. What kind of links might these be? “Vitamin K is an enzymatic cofactor that’s required for certain proteins to function,” Shea said. “One of these, osteocalcin, is the predominant non-collagenous protein in bone.”

Osteocalcin forms a soft, string-like material inside the mineralized portion of the bone, and helps make the bone matrix as a whole less brittle, Hernandez said. “Right now, a lot of treatments for osteoporosis focus on improving bone mineral density, but there are not a lot of ways to improve bone matrix quality,” he said. “What if we could change the gut microbiome so it makes more vitamin K, which could give people those benefits without having to eat more kale or take a regular vitamin supplement?”

Hernandez and Shea’s most recent results were published in the journal BONE and they are applying for a grant from the National Institutes of Health to do research to confirm that vitamin K is indeed responsible for the bone changes in mice with modified microbiomes. “It’s intriguing and we have a long way to go to get to that point, but if possible, it would be very cool,” Shea said. “It’s been a great collaboration —it’s fun to work with people who are interested in vitamin K.”

Hernandez predicts the collaboration will be a fruitful one. “The microbiome is an exciting new arena with a lot of potential for new treatments, and a lot of that is the interaction with nutritional components,” Hernandez said. “What’s going on at this center at Tufts is really going to be key to making these microbiome therapies work.”

Adequate sleep may optimize immune function, guard against coronavirus

University of Queensland (Australia), May 7, 2020

Those who want to give their body another layer of protection against infection by pathogens, such as the coronavirus, may want to catch up on their sleep. According to researchers at the University of Queensland (UQ), this is because any decline in the quality and quantity of sleep can negatively affect the body’s immunity. When a person’s immunity declines, it makes them more susceptible to illnesses, including those caused by deadly viruses.

“During sleep, the immune system releases proteins called cytokines. Certain cytokines are important for fighting infections and inflammation and help us respond to stress. But when we don’t get enough sleep or our sleep is disrupted, our bodies produce fewer of these important cytokines,” explained the researchers in an article they wrote for The Conversation.

In their column, the researchers cited a study published in the Archives of Internal Medicine that explored the link between sleeping habits and immunity.

A research team led by Sheldon Cohen of Carnegie Mellon University exposed 78 men and 75 women to the rhinovirus — the virus that causes the common cold — and monitored them for the development of a clinical cold.

As detailed in their paper, the researchers found that those who slept less than seven hours per night were almost three times more likely to develop a cold than those who slept eight hours or more per night.

According to the UQ researchers, while there is still not enough solid research on the relationship between sleep and the coronavirus, a pattern similar to the one reported by Cohen and his team can be expected.

3D brain-like tissue model links Alzheimer’s disease with herpes

Tufts University, May 6, 2020

Engineers and scientists led by Tufts University used a three-dimensional (3D) human tissue culture model mimicking the components and conditions in the brain to demonstrate a possible causal relationship between sporadic Alzheimer’s disease and herpes simplex virus I infection (HSV-1). Reported today in Science Advances, the model will allow for further studies into the causes and possible treatments of this devastating neurodegenerative condition.

After infecting neurons in the bioengineered brain model with HSV-1, the researchers observed formation of amyloid plaques, neuronal loss, neuroinflammation and diminished neural network functionality, all typical features of Alzheimer’s disease. Treatment of the brain tissue models with the antiviral drug valacyclovir resulted in reduced plaque formation and other markers of the disease.

Studies by other researchers have implicated pathogens as environmental agents possibly causing the development of Alzheimer’s disease, with a number of studies pointing to HSV-1.

“Our brain tissue model allowed us to take a closer look at the potential causal relationship between herpes and Alzheimer’s disease, and the results were intriquing,” said David Kaplan, Stern Family Professor of Engineering and chair of the Department of Biomedical Engineering at Tufts’ School of Engineering. “After just 3 days of herpes infection, we saw large and dense plaque formations of beta amyloid protein, as well as increased expression of some of the enzymes responsible for generating the plaques. We observed neuron loss, neuroinflammation and depressed signaling between neurons – everything we observe in patients. Never before have so many facets of the disease been replicated in vitro.”

The researchers found that 40 Alzheimer’s-associated genes were over-expressed in the HSV-1 infected brain tissue constructs compared to non-infected tissue. Prominent among them were genes coding for the enzymes cathepsin G and BACE2, both known to be associated with Alzheimer’s disease and involved in the production of beta amyloid peptides found in plaques. Some of these overexpressed gene products observed in the tissue model could become targets for future drug candidates.

“This is a model of Alzheimer’s disease which is very different from what other studies have used,” said Dana Cairns, postdoctoral research associate in David Kaplan’s lab and first author of the study. “Most other studies relied on using genetic mutations in the neurons to induce Alzheimer’s disease-like phenotypes and ours does not, which is what really sets it apart. Our model using normal neurons allows us to show that herpes virus alone is sufficient to induce Alzheimer’s disease phenotypes.”

Valacyclovir, which mitigated Alzheimer’s disease-like features in the brain tissue model, is an FDA approved anti-viral medication used to treat herpes infections. The drug also reduced expression back to pre-infection levels of several molecules and enzymes associated with Alzheimer’s disease, such as presenilin-1. The tissue model is set up to facilitate large scale screening of therapeutic or preventive drug candidates that target the earliest onset of this complex and devastating disease.

The 3D construct consists of a 6mm wide donut-shaped, sponge-like material made up of silk protein and collagen and populated with normal neural stem cells that are then guided to differentiate into neurons. The “donut ring” fosters the growth of neurons with the cell bodies situated in the silk-collagen donut, while extending axons into the “donut hole,” making neural connections and mimicking both the grey matter and white matter of the brain, respectively. Researchers not only can observe physical and biological changes in the neurons in real time using imaging methods but also can monitor electrical activity and integrity of the communication networks between the cells.

The model is particularly well suited for studying the origins of diseases. Most other existing in vitro models make use of cells from patients with early-onset Alzheimer’s disease, which accounts for only 1 to 6 percent of patients, cells derived from tumors, or induced to overexpress factors that push them into a disease state.

However, the genetic anomalies of these cells do not necessarily represent what happens in sporadic disease, which occurs without genetic inheritance and from as yet unknown causes in 95 percent of cases. These patients start with presumably normal brain tissue, with some likely age-related risk factors. Environmental conditions are suspected of playing a more significant role in triggering the cascade of molecular reactions leading to the onset of disease. The model used in this study starts with genetically normal cells, allowing for a clearer examination of environmental factors potentially leading to disease.

Anti‐inflammatory and antioxidant activity of carvacrol in the respiratory system: A systematic review and meta‐analysis

Federal University of Sergipe (Brazil) 06 April 2020

Abstract

Carvacrol is a monoterpene present in the essential oil of a number of plants and has been widely used in traditional medicine because it is considered to have a range of therapeutic effects including in relation to respiratory disease. To conduct a systematic review and meta‐analysis to assess the anti‐inflammatory and antioxidant activities of carvacrol when used in the treatment of respiratory disorders. A comprehensive literature search using Scopus, MEDLINE‐PubMed, Cochrane and Web of Science was undertaken. Papers related to the anti‐inflammatory or antioxidant properties of carvacrol in the treatment of an injury in the respiratory system in in vivo studies and published in the period up to and including August 2019. A total of 152 studies were initially identified, with only 17 meeting the inclusion criteria. Five of the studies were performed in humans, and 12 were performed in rodents. Among the 17 studies included in the systematic review, we performed the meta‐analysis with nine of the studies with animals. Carvacrol had a positive effect on the reduction of interleukin (IL)‐1β, IL‐4, IL‐8 and malondialdehyde (MDA); however, the analysis indicated that carvacrol had no effect on IL‐6 and tumor necrosis factor alpha (TNF‐α), probably due to the methodological quality of the studies and their heterogeneity. Current evidence supports the antioxidant and anti‐inflammatory effects of carvacrol, but its relationship with the reduction of some inflammatory mediators in animals with lung injury needs further elucidation.

Apples contain about 100 million bacteria, but organic apples are still good for gut health and the environment

Graz University of Technology (Austria), May 7, 2020

A recent study in Frontiers in Microbiology showed that apples can contain as many as 100 million bacterial cells – and that organic apples contained more beneficial bacteria than conventional or store-bought ones. The study also showed that store-bought apples not only lacked these beneficial bacteria, these also harbored bacteria strains that are known pathogens.

Gut bacteria help improve health and prevent chronic diseases

The human gut microbiome is comprised of trillions of bacteria, fungi and other microscopic organisms. But unlike the pathogenic bacteria that cause infection and disease, these microbes help maintain gut health and protect the gastrointestinal tract from inflammation and other abnormalities.

For instance, common gut problems like indigestion, abdominal cramps and constipation are often due to an imbalance in the gut microbiome. Bacterial communities in the gut also aid immune functions and boost metabolic processes. Studies also suggest that gut bacteria help reduce the amount of “bad” cholesterol in the blood, which increases the risk of heart disease.

Given the different integral functions of gut bacteria, it is important to maintain optimal gut health. To do this, most people consume fermented foods that contain tons of beneficial microbes or probiotics, such as Lactobacillus bulgaricus, Streptococcus thermophilus and Saccharomyces cerevisiae (yeast).

Some fruits like apples, bananas, blueberries and pears are also prized for their probiotics and high fiber content that help boost gut health.

Organic apples contain beneficial bacteria

A team of researchers from the Graz University of Technology in Austria found that organic apples harbor a large number of bacteria. But unlike pathogenic genera that cause a host of diseases, these bacteria might benefit gut health.

The researchers used microbial deoxyribonucleic acid (DNA) extraction and gene sequencing technologies to determine the strains of bacteria found in the different parts of the apple. The team used the Arlet apple, a popular variety in Austria, and examined both organic and conventional varieties.

The findings revealed that the seeds, stem, pulp and calyx contained the most number of bacteria. The researchers estimated that each of the eight apples sampled (four per group) contained about 100 million bacteria. And although the seeds are responsible for the distribution of these bacteria, the researchers stated that the plant’s surrounding environment might also be a major source of the microbes.

Moreover, the researchers noted that although the organic and conventional apples harbored the same number of bacteria, the composition of the bacteria differed. Organic apples had a more diverse collection of bacteria that included the beneficial Lactobacillus, a genus of bacteria found in fermented foods like yogurt and pickles.

The peel and pulp, in particular, contained large numbers of Methylobacterium, a type of bacteria used to promote plant growth. Past research has also shown that Methylobacterium can stimulate the flavor compounds in strawberries. Hence, the researchers suggest that this same bacterium might also contribute to the sweeter flavor of the organic apples.

On the other hand, conventional apples had pathogenic genera like Erwinia and Escherichia. Bacteria of the genus Erwinia are often linked to root rot, while Escherichia bacteria are known to cause intestinal infections and diarrhea. The conventional apples also did not contain as much beneficial bacteria as the organic ones.

The researchers suggested that the bacterial diversity in the organic apples might help limit the abundance of pathogens in the human gut. They thus concluded that organic apples provide benefits for the consumers more than the conventional varieties, which were found to harbor food-borne pathogens. Furthermore, the cultivation of organic apples might also be more beneficial to the environment.

Organic apples contain 100 million beneficial bacteria. Although little is known about the bacterial profile of other fruits, it’s best to stick to fresh and organic produce from local grocers and farmers.

Study finds that yoga and meditation can help minimize cognitive impairment

UCLA, May 10, 2020

Inner peace and a flexible body may not be the most valuable benefits that yoga and meditation have to offer, suggests new research by a UCLA-led team of neuroscientists.

The team found that a three-month course of yoga and meditation practice helped minimize the cognitive and emotional problems that often precede Alzheimer’s disease and other forms of dementia—and that it was even more effective than the memory enhancement exercises that have been considered the gold standard for managing mild cognitive impairment.

“Memory training was comparable to yoga with meditation in terms of improving memory, but yoga provided a broader benefit than memory training because it also helped with mood, anxiety and coping skills,” said Helen Lavretsky, the study’s senior author and a professor in residence in UCLA’s department of psychiatry.

People with mild cognitive impairment are two-and-a-half times more likely to develop Alzheimer’s disease and other forms of dementia. The study, which appears May 10 in the Journal of Alzheimer’s Disease, is the first to compare outcomes from yoga and meditation with those from memory training, which incorporates activities ranging from crossword puzzles to commercially available computer programs. The study of 25 participants, all over the age of 55, measured changes not just in behavior but also in brain activity.

“Historically and anecdotally, yoga has been thought to be beneficial in aging well, but this is the scientific demonstration of that benefit,” said Harris Eyre, the study’s lead author, a doctoral candidate at Australia’s University of Adelaide and a former Fulbright scholar at UCLA’s Semel Institute for Neuroscience and Human Behavior. “We’re converting historical wisdom into the high level of evidence required for doctors to recommend therapy to their patients.”

Lavretsky and Eyre studied participants who had reported issues with their memory, such as tendencies to forget names, faces or appointments or to misplace things. Subjects underwent memory tests and brain scans at the beginning and end of the study.

Eleven participants received one hour a week of memory enhancement training and spent 20 minutes a day performing memory exercises—verbal and visual association and other practical strategies for improving memory, based on research-backed techniques. The other 14 participants took a one-hour class once a week in Kundalini yoga and practiced 20 Kirtan Kriya meditation at home for 20 minutes each day. Kirtan Kriya, which involves chanting, hand movements and visualization of light, has been practiced for hundreds of years in India as a way to prevent cognitive decline in older adults, Lavretsky said.

After 12 weeks, the researchers saw similar improvements among participants in both groups in verbal memory skills—which come into play for remembering names and lists of words. But those who had practiced yoga and meditation had better improvements than the other subjects in visual-spatial memory skills, which come into play for recalling locations and navigating while walking or driving. The yoga-meditation group also had better results in terms of reducing depression and anxiety and improving coping skills and resilience to stress. That’s important because coming to terms with cognitive impairment can be emotionally difficult.

“When you have memory loss, you can get quite anxious about that and it can lead to depression,” said Lavretsky, who is also a researcher at the Semel Institute.

The researchers report that the participants’ outward improvements in memory corresponded with perceptible changes in their brain activity. Using functional magnetic resonance imaging, they showed that subjects in both groups had changes in their brain connectivity, but the changes among the yoga group were statistically significant, whereas the changes in the memory group were not.

The researchers attribute the positive “brain fitness” effects of mindful exercise to several factors, including its abilities to reduce stress and inflammation, improve mood and resilience, and enhance production of brain-derived neurotrophic growth factor, a protein the stimulates connections between neurons and kick-start telomerase activity, a process that replaces lost or damaged genetic material.

“If you or your relatives are trying to improve your memory or offset the risk for developing memory loss or dementia, a regular practice of yoga and meditation could be a simple, safe and low-cost solution to improving your brain fitness,” Lavretsky said.

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