How vitamins, steroids and potential antivirals might affect SARS-CoV-2

Evidence is emerging that vitamin D - and possibly vitamins K and A - might help combat COVID-19. A new study from the University of Bristol published in the journal of the German Chemical Society Angewandte Chemie has shown how they - and other antiviral drugs - might work. The research indicates that these dietary supplements and compounds could bind to the viral spike protein and so might reduce SARS-CoV-2 infectivity. In contrast, cholesterol may increase infectivity, which could explain why having high cholesterol is considered a risk factor for serious disease.

Recently, Bristol researchers showed that linoleic acid binds to a specific site in the viral spike protein, and that by doing so, it locks the spike into a closed, less infective form. (Linoleic acid is the predominant n-6 polyunsaturated fatty acid (PUFA) in the Western diet and we can obtain it from vegetable oils such as sunflower, safflower, soybean, corn, and canola oils as well as nuts and seeds.) 

Now, a research team has used computational methods to search for other compounds that might have the same effect, as potential treatments. They hope to prevent human cells becoming infected by preventing the viral spike protein from opening enough to interact with a human protein (ACE2). New anti-viral drugs can take years to design, develop and test, so the researchers looked through a library of approved drugs and vitamins to identify those which might bind to this recently discovered 'druggable pocket' inside the SARS-CoV-2 spike protein.

The team first studied the effects of linoleic acid on the spike, using computational simulations to show that it stabilizes the closed form. Further simulations showed that dexamethasone - which is an effective treatment for COVID-19 - might also bind to this site and help reduce viral infectivity in addition to its effects on the human immune system.

The team then conducted simulations to see which other compounds bind to the fatty acid site. This identified some drugs that have been found by experiments to be active against the virus, suggesting that this may be one mechanism by which they prevent viral replication such as, by locking the spike structure in the same way as linoleic acid.

The findings suggested several drug candidates among available pharmaceuticals and dietary components, including some that have been found to slow SARS-CoV-2 reproduction in the laboratory. These have the potential to bind to the SARS-CoV-2 spike protein and may help to prevent cell entry.

The simulations also predicted that the fat-soluble vitamins D, K and A bind to the spike in the same way making the spike less able to infect cells.

Dr Deborah Shoemark, Senior Research Associate (Biomolecular Modelling) in the School of Biochemistry, who modelled the spike, explained: "Our findings help explain how some vitamins may play a more direct role in combatting COVID than their conventional support of the human immune system.

"Obesity is a major risk factor for severe COVID. Vitamin D is fat soluble and tends to accumulate in fatty tissue. This can lower the amount of vitamin D available to obese individuals. Countries in which some of these vitamin deficiencies are more common have also suffered badly during the course of the pandemic. Our research suggests that some essential vitamins and fatty acids including linoleic acid may contribute to impeding the spike/ACE2 interaction. Deficiency in any one of them may make it easier for the virus to infect."

Pre-existing high cholesterol levels have been associated with increased risk for severe COVID-19. Reports that the SARS-CoV-2 spike protein binds cholesterol led the team to investigate whether it could bind at the fatty acid binding site. Their simulations indicate that it could bind, but that it may have a destabilising effect on the spike's locked conformation, and favour the open, more infective conformation.

Dr Shoemark continued: "We know that the use of cholesterol lowering statins reduces the risk of developing severe COVID and shortens recovery time in less severe cases. Whether cholesterol de-stabilises the "benign", closed conformation or not, our results suggest that by directly interacting with the spike, the virus could sequester cholesterol to achieve the local concentrations required to facilitate cell entry and this may also account for the observed loss of circulating cholesterol post infection."

Professor Adrian Mulholland, of Bristol's School of Chemistry, added: "Our simulations show how some molecules binding at the linoleic acid site affect the spike's dynamics and lock it closed. They also show that drugs and vitamins active against the virus may work in the same way. Targeting this site may be a route to new anti-viral drugs. A next step would be to look at effects of dietary supplements and test viral replication in cells."

Alison Derbenwick Miller, Vice President, Oracle for Research, said: "It's incredibly exciting that researchers are gaining new insights into how SARS-CoV-2 interacts with human cells, which ultimately will lead to new ways to fight COVID-19. We are delighted that Oracle's high-performance cloud infrastructure is helping to advance this kind of world-changing research. Growing a globally-connected community of cloud-powered researchers is exactly what Oracle for Research is designed to do."

The team included experts from Bristol UNCOVER Group, including Bristol's Schools of Chemistry, Biochemistry, Cellular and Molecular Medicine, and Max Planck Bristol Centre for Minimal Biology, and Bristol Synthetic Biology Centre, using Bristol's high performance computers and the UK supercomputer, ARCHER, as well as Oracle cloud computing. The study was supported by grants from the EPSRC and the BBSRC.

Easy to follow time restricted eating weight loss plan works

 A pilot study of time restricted eating, in which food is consumed only within a daily eight-hour period, has shown that the plan is simple, easy to follow, and that weight loss is at least as good as that achieved through more complex dietary interventions.

Fifty participants with obesity attempted to follow the plan for 12 weeks. Telephone surveys were conducted weekly, and at 6 and 12 weeks participants attended the clinic to be weighed. Almost 60% of participants were still following time restricted eating at three months, and had lost an average of 3.5kg, but even those who did not manage full adherence also lost weight.

The researchers from Queen Mary University of London say that the adherence and weight loss results are encouraging enough to warrant a randomised trial with long term follow-up.

Corresponding author Dunja Przulj from Queen Mary University of London said: "Simple weight management plans which people can stick to are currently lacking. In this study, more than a quarter of the participants had lost at least 5% of their starting body weight at 12 weeks."

Antibiotic overuse

 

The overuse of antibiotics occurs due to the mistaken widespread belief that they are beneficial for a broad array of conditions and because many physicians are willing to prescribe antibiotics if patients ask for the medication, according to a Rutgers study.

The study, published in the journal BioEssays, reviewed more than 200 peer-reviewed studies to examine the causes behind antibiotic overuse, which can lead harmful bacteria to become drug-resistant and cause harmful effects on the microbiome, the collection of beneficial germs that live in and on our bodies.

Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers and lead author, said the global use of antibiotics between 2000 and 2015 increased 39 percent, with a 77 percent increase in low- and middle-income countries. He discusses the study's findings.

What health concerns result from the disruption of the microbiome by antibiotics?

In children, improper antibiotic use can alter the microbiome while their immunological, metabolic and neural systems are developing. Epidemiological studies associate antibiotic exposure with an increased risk of disease of allergic, metabolic and cognitive disorders that have grown more common in children during the antibiotic era.

In adults, there is increasing evidence that antibiotics may enhance risk for metabolic and neoplastic diseases, including diabetes, kidney stones and growths in the colon and rectum that can lead to cancer.

What are the trends you found in antibiotic use?

Studies in the United States, United Kingdom and China found numerous online pharmacies selling antibiotics without a prescription. This problem also is large in Iow- to middle-income countries, where 60 percent of antibiotics are sold without prescriptions, often by untrained medical practitioners.

Perhaps of special concern during the COVID-19 pandemic is the finding that telemedicine services are another potential source of questionable antibiotic sales in the United States. A recent analysis found that patients with acute respiratory infections were more often prescribed broad-spectrum antibiotics if they had a tele-health doctor visit, compared to an in-person visit.

Worldwide, antibiotic use is highest in young children, especially in low-income areas. This is often in response to the fact that young children are prone to have four to six upper respiratory tract infections each year. Although most of these infections are treated by antibiotics, 80 percent are not caused by bacteria and would therefore derive no benefit from antibiotics.

Are some practitioners more likely to prescribe antibiotics?

Our findings are consistent with the hypothesis that older physicians are more likely than their younger colleagues to prescribe antibiotics. For example, one study found that physicians over 30 were several times more likely to prescribe antibiotics for common respiratory conditions that do not necessarily require them. Another study found that physicians with over 25 years in practice were disproportionately likely to issue prescriptions of more than eight days.

What misinformation did you find among the public?

Many people believe that antibiotics are effective against bacterial and viral illnesses, lumping all types of pathogens together and adopting a "germs are germs" attitude. Others believe that taking antibiotics can't hurt. Across Europe, for example, 57 percent of people surveyed were unaware that antibiotics were ineffective against viruses, and 44 percent did not know that antibiotics have no effect against colds or influenza.

What other reasons did you find for inappropriate prescription of antibiotics?

Antibiotics are commonly used across the world to self-treat health problems for which they were never intended, such as in Nigeria, where women are increasingly using antibiotics to reduce menstrual cramps. In low- to middle-income countries, antibiotics are often seen as strong, magical medicines, capable of both curing and preventing a range of illness. In many countries people also take them to return to work or school when ill. One of the studies found that 63 percent of Chinese university students kept a personal antibiotic stock at home.

Parents may appeal for an antibiotic for their children so that they can go to work or for the children to return to school or daycare. A U.S. study found that 43 percent of parents of a child with cold symptoms believed that antibiotics were necessary.

In addition, some doctors are inclined to prescribe an antibiotic to maintain a good relationship with patients who expect to receive medication. Patients may not demand antibiotics outright, but rather infer their need for them by how they describe the severity of their illness or note that they worked in the past for a similar issue. People have become less willing to wait and let an illness run its course. The perception that there is a pill for ills of all kinds leads the public to demand immediate relief for symptoms from practitioners and to self-medicate.

Every time an antibiotic is given, money changes hands. This is especially a problem in low- and middle-income countries, where pharmacists are happy to dispense without a prescription to their customers. The rural health practitioners in China are paid every time they dispense an antibiotic as well. Such monetary incentives favor the wide use of antibiotics.

How can antibiotic overuse be addressed?

Clinicians need to be better educated about the long-term effects on the microbiome and learn about better ways to speak with their patients about antibiotic risks and benefits. They also need to improve their communication about the consequences of antibiotic treatments and identify antibiotic alternatives.

Juicing technique could influence healthfulness of fresh-squeezed juice

 With the New Year, many people are making resolutions to eat healthier, by eating more vegetables, for example. But those who don't like the taste or texture of some vegetables might prefer to drink them in a home-squeezed juice. Now, researchers reporting in ACS Food Science & Technology have found that the choice of household juicing technique can influence the phytochemical content and antioxidant activity of common vegetable juices.

Home juicing machines have become popular in recent years, with different types available. For example, blenders crush vegetables with fast, spinning blades, and the resulting juice is typically thick, with much pulp and dietary fiber. In contrast, high-speed centrifugal juicers quickly pulverize veggies and separate out pulp and fiber, making for a thinner juice. Low-speed juice extractors squeeze juice with a horizontal auger that rotates vegetables at a low speed, producing the least heat of the three methods and also removing pulp and fiber. Juicing can alter the levels of health-promoting phytochemicals and antioxidants in raw vegetables by exposing inner tissues to oxygen, light and heat and releasing enzymes. Therefore, Junyi Wang, Guddadarangavvanahally Jayaprakasha and Bhimanagouda Patil at Texas A&M University wanted to compare the phytochemical and antioxidant contents of 19 vegetables juiced with these three techniques.

After preparing juices with the different methods, the researchers observed that, in general, blending produced juices with the lowest amounts of some beneficial compounds, such as vitamin C, antioxidants and phenolics, probably because the technique produced the most heat. Low-speed juicing generated the highest amounts of beneficial compounds, although exceptions were found for certain vegetables. However, likely because of their higher fiber content, blended vegetable juices had the highest amounts of α-amylase inhibitors, which could help reduce hyperglycemia after a meal. The researchers then used mass spectrometry and chemometrics to identify and quantify 85 metabolites in juices prepared by the three methods, finding that the low-speed juicer produced more diverse metabolites than the other two methods, but the relative abundances for the three juicing methods differed based on the veggie type. Therefore, different vegetables and juicing methods could produce unique health benefits, the researchers say.

Afternoon napping linked to better mental agility

 Taking a regular afternoon nap may be linked to better mental agility, suggests research published in the online journal General Psychiatry.

It seems to be associated with better locational awareness, verbal fluency, and working memory, the findings indicate.

Longer life expectancy and the associated neurodegenerative changes that accompany it, raise the prospect of dementia, with around 1 in 10 people over the age of 65 affected in the developed world.

As people age, their sleep patterns change, with afternoon naps becoming more frequent. But research published to date hasn't reached any consensus on whether afternoon naps might help to stave off cognitive decline and dementia in older people or whether they might be a symptom of dementia.

The researchers explored this further in 2214 ostensibly healthy people aged at least 60 and resident in several large cities around China, including Beijing, Shanghai, and Xian.

In all, 1534 took a regular afternoon nap, while 680 didn't. All participants underwent a series of health checks and cognitive assessments, including the Mini Mental State Exam (MMSE) to check for dementia.

The average length of night time sleep was around 6.5 hours in both groups.

Afternoon naps were defined as periods of at least five consecutive minutes of sleep, but no more than 2 hours, and taken after lunch. Participants were asked how often they napped during the week; this ranged from once a week to every day.

The dementia screening tests included 30 items that measured several aspects of cognitive ability, and higher function, including visuo-spatial skills, working memory, attention span, problem solving, locational awareness and verbal fluency.

The MMSE cognitive performance scores were significantly higher among the nappers than they were among those who didn't nap. And there were significant differences in locational awareness, verbal fluency, and memory.

This is an observational study, and so can't establish cause. And there was no information on the duration or timing of the naps taken, which may be important.

But there are some possible explanations for the observations found, say the researchers.

One theory is that inflammation is a mediator between mid-day naps and poor health outcomes; inflammatory chemicals have an important role in sleep disorders, note the researchers.

Sleep regulates the body's immune response and napping is thought to be an evolved response to inflammation; people with higher levels of inflammation also nap more often, explain the researchers.

Higher omega-3 blood levels may reduce risk for death from COVID-19 infection

 Researchers with the Fatty Acid Research Institute (FARI) and collaborators at Cedars-Sinai Medical Center in Los Angeles and in Orange County, CA, have published the first direct evidence that higher omega-3 blood levels may reduce risk for death from COVID-19 infection. The report was published in the journal Prostaglandins, Leukotrienes and Essential Fatty Acids on January 20, 2021.

There are several papers in the medical literature hypothesizing that omega-3 fatty acids should have beneficial effects in patients with COVID-19 infection, but up until now, there have been no published peer-reviewed studies supporting that hypothesis.

This study included 100 patients admitted to the hospital with COVID-19 for whom admission blood samples had been stored. Clinical outcomes for these patients were obtained and blood was analyzed for the Omega-3 Index (O3I, red blood cell membrane EPA+DHA levels) at OmegaQuant Analytics (Sioux Falls, SD). Fourteen of the patients died.

The 100 patients were grouped into four quartiles according to their O3I, with 25% of the patients in each quartile. There was one death in the top quartile (i.e., 1 death out of 25 patients with O3I>5.7%), with 13 deaths in the remaining patients (i.e., 13 deaths out of 75 patients with O3I<5.7%).

In age-and-sex adjusted regression analyses, those in the highest quartile (O3I >5.7%) were 75% less likely to die compared with those in the lower three quartiles (p=0.07). Stated another way, the relative risk for death was about four times higher in those with a lower O3I (<5.7%) compared to those with higher levels.

"While not meeting standard statistical significance thresholds, this pilot study - along with multiple lines of evidence regarding the anti-inflammatory effects of EPA and DHA - strongly suggests that these nutritionally available marine fatty acids may help reduce risk for adverse outcomes in COVID-19 patients. Larger studies are clearly needed to confirm these preliminary findings," said Arash Asher, MD, the lead author on this study.

Agreeing with Dr. Asher, cardiology researcher and co-developer with Dr. Harris of the Omega-3 Index, Clemens von Schacky, MD, (CEO, Omegametrix GmbH, Martinsried, Germany, and not involved with the study) said, "Asher et al have demonstrated that a low Omega-3 Index might be a powerful predictor for death from COVID-19. Although encouraging, their findings clearly need to be replicated."

Omega-3 expert James H. O'Keefe, Jr., MD, (Director of Preventive Cardiology, Saint Luke's Mid America Heart Institute, Kansas City, MO, and also not involved with the study) observed, "An excessive inflammatory response, referred to as a 'cytokine storm,' is a fundamental mediator of severe COVID-19 illness. Omega-3 fatty acids (DHA and EPA) have potent anti-inflammatory activities, and this pilot study provides suggestive evidence that these fatty acids may dampen COVID-19's cytokine storm."

No cardiovascular benefits to dietary supplements except B vitamins

According to research reported in the Journal of the American College of Cardiology (JACC) the evidence continued to show no cardiovascular benefits to dietary supplements except B vitamins. No cardiovascular or mortality effects were seen with multivitamins, vitamin D, calcium, or vitamin C in a meta-analysis incorporating 156 randomized controlled trials and meta-analyses. Moderate-quality evidence was available associating folic acid (vitamin and B vitamins with reduced stroke risk,  Niacin was tied to increased all-cause mortality when taken with background statins.

New research reported in the Journal of the American College of Cardiology (JACC). Has found that vitamin D supplements "do not benefit cardiovascular health in the general population and therefore should not be taken for this purpose…Even the benefits of supplemental vitamin D on bone health appear overstated for the general population," The researchers, also found calcium to be potentially harmful. These two supplements, often taken together for bone health, had no heart benefits when looking at the totality of observational and randomized studies such as ViDA and the more definitive VITAL trial.

C offee temporarily counteracts effect of sleep loss on cognitive function

A new study exploring the impact of repeated sleep loss during a simulated working week has found that consuming caffeinated coffee during the day helps to minimize reductions in attention and cognitive function, compared to decaffeinated coffee1.

While this effect occurred in the first three-to-four days of restricted sleep, by the fifth and final day, no difference was seen between caffeinated and decaffeinated coffee drinkers. This therefore suggests that the beneficial effects of coffee for people with restricted sleep are temporary1.

It is estimated that over 30% of adult Western populations sleep less than the recommended seven to eight hours on weekday nights and 15% regularly sleep less than six hours2,3. This can have a considerable impact on people's health and wellbeing, including causing sleepiness and impairing vigilance and attention4.

Denise Lange, study co-author, commented: "Previous research suggests that acute consumption of caffeinated coffee can reduce the impact of sleep deprivation on deficits of attention and cognitive function in a short-term setting. This study is among the first to examine whether this effect can be translated into a real-world situation, where caffeinated drinks are commonly consumed every day by people who experience chronic sleep restriction. Our study indicates that moderate coffee intake can mitigate some repercussions of reduced sleep over a few days, however, this is not a substitute for a good night's sleep in the long term."

The study was conducted at the state-of-the-art Institute of Aerospace Medicine, in Cologne Germany. 26 participants carrying a distinct genotype of the gene encoding the adenosine A2A receptor were randomly assigned to groups either drinking caffeinated coffee (containing 300 mg caffeine) or decaffeinated coffee under double-blind conditions. During five days, the sleep of all participants was restricted to five hours per night and each day they rated their subjective sleepiness and were tested on levels of vigilance, alertness, reaction-time, accuracy and memory1.

###

Notes to editors

• Moderate coffee consumption can be defined as 3-5 cups per day, based on the European Food Safety Authority's review of caffeine safety5.

Daily aspirin use does not reduce risk of colorectal cancer among adults who begin taking it after age 70

 

Regular aspirin use has clear benefits in reducing colorectal cancer incidence among middle-aged adults, but also comes with some risk, such as gastrointestinal bleeding. And when should adults start taking regular aspirin and for how long?

There is substantial evidence that a daily aspirin can reduce risk of colorectal cancer in adults up to age 70. But until now there was little evidence about whether older adults should start taking aspirin.

A team of scientists set out to study this question. They were led by Andrew T. Chan MD, MPH, a gastroenterologist and chief of the Clinical and Translational Epidemiology Unit at Massachusetts General Hospital (MGH). Their report appears in JAMA Oncology.

The researchers carried out a pooled analysis of two large U.S. cohort studies: The Nurses' Health Study (January 1980 - June 2014) and the Health Professionals Follow-up Study (January 1986 - January 2014). These two studies contributed data on more than 94,500 participants' use of aspirin over about 35 years, offering a unique opportunity to understand the effect of aspirin use across the lifespan on cancer risk.

The researchers found that regular aspirin use was linked to lower colorectal cancer risk among people aged 70 or older. However, this advantage was only significant among people who started taking aspirin before the age of 70. People who started regular aspirin use at the age of 70 or older did not seem to reap any benefit.

"There is considerable evidence that aspirin can prevent colorectal cancer in adults between 50 and 70 years old," says Chan. "But it has not been clear whether the effect is similar in older adults."

Aspirin is considered the most well-established agent that protects against colorectal cancer (CRC). It is currently recommended by the U.S. Preventive Services Task Force for people aged 50-59 years with specific cardiovascular risk profiles because of its protective effect against heart disease.

However, the recent Aspirin in Reducing Events in the Elderly (ASPREE) trial reported that participants who took a daily low dose of aspirin (100 mg) after age 70 for about five years actually had an unexpected 30% higher risk of death from cancer. The vast majority of the ASPREE participants (89%) had never taken aspirin regularly before joining the study. Chan's team also recently reported that ASPREE participants on aspirin did not experience an increase or decrease in risk of developing a cancer despite having an increase in risk of death from cancer.

That led to the question: Does regular aspirin benefit or harm people older than 70 and does it matter when aspirin was started?

The current study confirms that initiating aspirin at an older age was not associated with a lower risk of colorectal cancer. However, importantly, there is a potential benefit of continuing aspirin if is started at an earlier age. These results, the researchers say, "strongly suggest that there is a potential biological difference in the effect of aspirin at older ages which requires further research."

Adds Chan: "As people get older, if they are not already taking aspirin, a discussion is warranted about whether to start aspirin after weighing the benefits against the risks."

Metformin use reduces risk of death for patients with COVID-19 and diabetes

Use of the diabetes drug metformin -- before a diagnosis of COVID-19 -- is associated with a threefold decrease in mortality in COVID-19 patients with Type 2 diabetes, according to a racially diverse study at the University of Alabama at Birmingham. Diabetes is a significant comorbidity for COVID-19. "This beneficial effect remained, even after correcting for age, sex, race, obesity, and hypertension or chronic kidney disease and heart failure," said Anath Shalev, M.D., director of UAB's Comprehensive Diabetes Center and leader of the study. "Since similar results have now been obtained in different populations from around the world -- including China, France and a UnitedHealthcare analysis -- this suggests that the observed reduction in mortality risk associated with metformin use in subjects with Type 2 diabetes and COVID-19 might be generalizable," Shalev said. How metformin improves prognosis in the context of COVID-19 is not known, Shalev says. The UAB findings suggest that the mechanisms may go beyond any expected improvement in glycemic control or obesity, since neither body mass index, blood glucose nor hemoglobin A1C were lower in the metformin users who survived as compared to those who died. "The mechanisms may involve metformin's previously described anti-inflammatory and anti-thrombotic effects," Shalev said. The study -- first made available in MedRxiv and now published in the peer-reviewed journal Frontiers in Endocrinology -- included 25,326 patients tested for COVID-19 at the tertiary care UAB Hospital between Feb. 25 and June 22 of last year. Of the 604 patients found to be COVID-19-positive, 311 were African Americans. The primary outcome in the study was mortality in COVID-19-positive subjects, and the potential association with subject characteristics or comorbidities was analyzed. Researchers found that Blacks, who are only 26 percent of Alabama's population, were 52 percent of those who tested positive for COVID-19, and only 30 percent of those who tested negative. In contrast, only 36 percent of the COVID-19-positive subjects were white, while whites made up 56 percent of those who tested negative, further underlining the racial disparity. Once COVID-19-positive though, no significant racial difference in mortality was observed. "In our cohort," Shalev said, "being African American appeared to be primarily a risk factor for contracting COVID-19, rather than for mortality. This suggests that any racial disparity observed is likely due to exposure risk and external socioeconomic factors, including access to proper health care." Overall mortality for COVID-19-positive patients was 11 percent. The study found that 93 percent of deaths occurred in subjects over the age of 50, and being male or having high blood pressure was associated with a significantly elevated risk of death. Diabetes was associated with a dramatic increase in mortality, with an odds ratio of 3.62. Overall, 67 percent of deaths in the study occurred in subjects with diabetes. The researchers looked at the effects of diabetes treatment on adverse COVID-19 outcomes, focusing on insulin and metformin as the two most common medications for Type 2 diabetes. They found that prior insulin use did not affect mortality risk. However, prior metformin use was a different matter. Metformin use significantly reduced the odds of dying, and the 11 percent mortality for metformin users was not only comparable to that of the general COVID-19-positive population, it was dramatically lower than the 23 percent mortality for diabetes patients not on metformin. After controlling for other covariates, age, sex and metformin use emerged as independent factors affecting COVID-19-related mortality. Interestingly, even after controlling for all these other covariates, death was significantly less likely -- with an odds ratio of 0.33 -- for Type 2 diabetes subjects taking metformin, compared with those who did not take metformin. "These results suggest that, while diabetes is an independent risk factor for COVID-19-related mortality," Shalev said, "this risk is dramatically reduced in subjects taking metformin -- raising the possibility that metformin may provide a protective approach in this high-risk population." The researchers say future studies will need to explore how metformin is protective, as well as assess the risks and benefits of metformin treatment and the indications for its use in the face of the ongoing COVID-19 pandemic.

Short term low carbohydrate diet linked to remission of type 2 diabetes

Patients with type 2 diabetes who follow a strict low carbohydrate diet for six months may experience greater rates of remission compared with other recommended diets without adverse effects, suggests a study published by The BMJ today. The researchers acknowledge that most benefits diminished at 12 months, but say doctors might consider short term strict low carbohydrate diets for managing type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed. Type 2 diabetes is the most common form of diabetes worldwide and diet is recognised as an essential part of treatment. But uncertainty remains about which diet to choose and previous studies have reported mixed results. To address this evidence gap, a team of international researchers set out to assess the effectiveness and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes, compared with (mostly low fat) control diets. Their findings are based on analysis of published and unpublished data from 23 randomised trials involving 1,357 participants. LCDs were defined as less than 26% daily calories from carbohydrates and VLCDs were defined as less than 10% daily calories from carbohydrates for at least 12 weeks in adults (average age 47 to 67 years) with type 2 diabetes. Outcomes were reported at six and 12 months and included remission of diabetes (reduced blood sugar levels with or without the use of diabetes medication), weight loss, adverse events and health related quality of life. Although the trials were designed differently, and were of varying quality, the researchers were able to allow for this in their analysis. Based on low to moderate certainty evidence, the researchers found that patients on LCDs achieved higher diabetes remission rates at six months compared with patients on control diets, without adverse events. For example, based on moderate certainty evidence from 8 trials with 264 participants, those following a LCD experienced, on average, a 32% absolute risk reduction (28 fewer cases per 100 followed) in diabetes remission at 6 months. LCDs also increased weight loss, reduced medication use, and improved body fat (triglyceride) concentrations at six months. However, most of these benefits diminished at 12 months, a finding consistent with previous reviews, and some evidence showed worsening of quality of life and cholesterol levels at 12 months. This study used robust methods to increase the precision and overall certainty of the effect estimates. But the authors acknowledge some limitations, such as the ongoing debate around what constitutes remission of diabetes, and uncertainty over the longer term effectiveness and safety of LCDs. They also stress that their results are based on moderate to low certainty evidence. As such, they suggest clinicians "might consider short term LCDs for management of type 2 diabetes, while actively monitoring and adjusting diabetes medication as needed." "Future long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes, as well as cardiovascular mortality and major morbidity," they conclude.

1 small alcoholic drink a day = an increased risk of atrial fibrillation

A study of nearly 108,000 people has found that people who regularly drink a modest amount of alcohol are at increased risk of atrial fibrillation, a condition where the heart beats in an abnormal rhythm. The study, published today (Wednesday) in the European Heart Journal [1], found that, compared to drinking no alcohol at all, just one alcoholic drink a day was linked to a 16% increased risk of atrial fibrillation over an average (median) follow-up time of nearly 14 years. This means that while four teetotallers in 100 might develop atrial fibrillation over the period of the study, five per 100 might develop the condition if they consumed alcohol starting with slightly more than an alcoholic drink a week and more than 75% of them consumed up to one drink a day [2]. The researchers categorised one alcoholic drink as containing 12 g of ethanol, which is the equivalent of a small (120 ml) glass of wine, a small beer (330 ml) or 40 ml of spirits. It is well known that people who drink a lot of alcohol regularly are at increased risk of developing heart failure, and heart failure can increase the incidence of atrial fibrillation. Several studies have shown a slightly higher risk of heart problems for people who never drink alcohol; they often show that this risk reduces for people who drink a modest amount, and then rises sharply the more alcohol is consumed, creating a 'J' shape on graphs. Until now, it has not been clear whether this was also the case for atrial fibrillation. However, in the current study led by Professor Renate Schnabel, a consultant cardiologist at the University Heart and Vascular Center, Hamburg-Eppendorf (Germany), researchers found that although low doses of alcohol were associated with a reduced risk of heart failure compared to teetotallers, a similar 'J' shape reduction in risk was not seen for atrial fibrillation. This suggests that the increased risk of atrial fibrillation among people drinking small amounts of alcohol was not triggered by heart failure. Prof. Schnabel said: "To our knowledge, this is the largest study on alcohol consumption and long-term incidence of atrial fibrillation in the community. Previous studies have not had enough power to examine this question, although they have been able to show a relationship between alcohol intake and other heart and blood vessel problems, such as heart attack and heart failure. In our study, we can now demonstrate that even very low regular alcohol consumption may increase the risk of atrial fibrillation. "These findings are important as the regular consumption of alcohol, the 'one glass of wine a day' to protect the heart, as is often recommended for instance in the lay press, should probably no longer be suggested without balancing risks and possible benefits for all heart and blood vessel diseases, including atrial fibrillation." The researchers analysed information on 107,845 people taking part in five community-based studies in Sweden, Norway, Finland, Denmark and Italy. The participants underwent medical examinations at the time they joined the studies between 1982 and 2010 and provided information on their medical histories, lifestyles (including alcohol and tobacco consumption), employment and education levels. A total of 100,092 participants did not have atrial fibrillation when they enrolled and their median age was nearly 48 years (range 24-97 years). During the median follow-up period of nearly 14 years, 5,854 people developed atrial fibrillation. The associations between alcohol consumption and the risk of atrial fibrillation were similar for all types of alcoholic drinks and for men and women. In addition to the 16% increased risk of atrial fibrillation compared to teetotallers seen in people who consumed only one alcoholic drink a day, the researchers found that the risk increased with increasing alcohol intake; up to two drinks a day was associated with a 28% increased risk and this went up to 47% for those who consumed more than four. The exact mechanisms by which modest amounts of alcohol could trigger atrial fibrillation are not known. Studies have shown that heavy drinking over a short period of time can trigger 'holiday heart syndrome' in some people, and in some atrial fibrillation patients, small amounts of alcohol can trigger arrhythmia episodes. Limitations of the study include the fact that study participants reported the type and quantity of alcohol they drank and this could lead to under-reporting; the information available did not enable the researchers to look at the effects of binge drinking; some episodes of atrial fibrillation can be asymptomatic and so may not have been reported; only adults across Europe were included in the analyses and so it may not be possible for the results to be generalised to other populations; as the study was observational, it can show only an association between alcohol intake and atrial fibrillation and not that alcohol causes atrial fibrillation. In an accompanying editorial [3], Jorge A. Wong and David Conen from the Population Health Research Institute at McMaster University, Hamilton, Canada, write that the research "makes an important contribution to our understanding of the relationship between alcohol intake and incident AF, in particular at the lower spectrum of alcohol consumption. A significant relationship between alcohol and AF was identified, and even small quantities of alcohol were associated with an increased, albeit small, risk of incident AF. "Together with a recent randomized trial showing that a reduction in alcohol intake led to a reduction in AF recurrence, these data suggest that lowering alcohol consumption may be important for both prevention and management of AF. Importantly, any reduction in low-to-moderate alcohol consumption to potentially prevent AF needs to be balanced with the potentially beneficial association low amounts of alcohol may have with respect to other cardiovascular outcomes . . . The net clinical benefit of consuming low amounts of alcohol requires further study, ideally in adequately powered randomized trials. Until then, each individual has to make its own best educated decision as to whether consuming up to one alcoholic drink per day is worthwhile and safe." Notes: [1] "Alcohol consumption, cardiac biomarkers and risk of atrial fibrillation and adverse outcomes," by Dora Csengeri et al. European Heart Journal. doi:10.1093/eurheartj/ehaa953 [2] Data on absolute risk are not given in the research paper. The absolute risk was calculated using further information from the researchers and the University of Cambridge Winton Centre for Risk and Evidence Communication RealRisk web tool: https://url.wintoncentre.uk/p6lcb [3] "Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance," by Jorge A. Wong and David Conen. European Heart Journal. doi:10.1093/eurheartj/ehaa955

Excess alcohol consumption linked to portion of cancer incidence and mortality

A new study finds that alcohol consumption accounts for a considerable portion of cancer incidence and mortality in all 50 states and the District of Columbia. The article, which appears in Cancer Epidemiology, states that the proportion of cancer cases attributable to alcohol consumption ranged from a high of 6.7% in Delaware to a low of 2.9% in Utah. Similarly, Delaware had the highest proportion of alcohol-related cancer deaths (4.5%) and Utah had the lowest (1.9%). This study conducted by Farhad Islami, MD, PhD, and colleagues at the American Cancer Society is the first to estimate contemporary proportions and counts of alcohol-attributable cancer cases and deaths for all states. Data shows the proportions were generally higher in New England and Western states and lower in Midwestern and Southern states. "This information is important for prioritizing state-level cancer prevention and control efforts to reduce alcohol consumption and the burden of alcohol-related cancers," said Dr. Islami. The proportion of alcohol-related cancers was far greater for some individual cancer types. For oral cavity/pharyngeal cancer cases, for example, it ranged from 36% in Utah to 62.5% in Delaware and was 45% or more in 45 states and the District of Columbia. By sex, alcohol-related cancer cases and deaths for most evaluated cancer types were higher among men, in part reflecting higher levels of alcohol consumption among men. In the U.S. on average, alcohol consumption accounted for 4.8% of cancer cases and 3.2% of cancer deaths, or about 75,200 cancer cases and 18,950 cancer deaths annually, during 2013 to 2016. In addition, the authors say, "healthcare providers and public health practitioners can educate the community to expand the currently limited awareness of the cancer-related risks of alcohol consumption." The American Cancer Society's guideline for Diet and Physical Activity for Cancer Prevention states that it is best not to consume alcohol; for those who do drink, consumption should be limited to no more than 1 drink per day for women and 2 drinks per day for men.

Low-fat, plant-based diet vs. low-carb, animal-based diet

People on a low-fat, plant-based diet ate fewer daily calories but had higher insulin and blood glucose levels, compared to when they ate a low-carbohydrate, animal-based diet, according to a small but highly controlled study at the National Institutes of Health. Led by researchers at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the study compared the effects of the two diets on calorie intake, hormone levels, body weight, and more. 

The findings, published in Nature Medicine, broaden understanding of how restricting dietary carbohydrates or fats may impact health. 

 "High-fat foods have been thought to result in excess calorie intake because they have many calories per bite. Alternatively, high-carb foods can cause large swings in blood glucose and insulin that may increase hunger and lead to overeating," said NIDDK Senior Investigator Kevin Hall, Ph.D., the study's lead author. "Our study was designed to determine whether high-carb or high-fat diets result in greater calorie intake." 

 The researchers housed 20 adults without diabetes for four continuous weeks in the NIH Clinical Center's Metabolic Clinical Research Unit. The participants, 11 men and nine women, received either a plant-based, low-fat diet or an animal-based, low-carbohydrate diet for two weeks, immediately followed by two weeks on the alternate diet. The low-fat diet was high in carbohydrates. The low-carbohydrate diet was high in fats. Both diets were minimally processed and had equivalent amounts of non-starchy vegetables. 

The participants were given three meals a day, plus snacks, and could eat as much as desired. The main results showed that people on the low-fat diet ate 550 to 700 fewer calories per day than when they ate the low-carb diet. Despite the large differences in calorie intake, participants reported no differences in hunger, enjoyment of meals, or fullness between the two diets. Participants lost weight on both diets, but only the low-fat diet led to a significant loss of body fat. 

 "Despite eating food with an abundance of high glycemic carbohydrates that resulted in pronounced swings in blood glucose and insulin, people eating the plant-based, low-fat diet showed a significant reduction in calorie intake and loss of body fat, which challenges the idea that high-carb diets per se lead people to overeat. On the other hand, the animal-based, low-carb diet did not result in weight gain despite being high in fat," said Hall. 

 These findings suggest that the factors that result in overeating and weight gain are more complex than the amount of carbs or fat in one's diet. For example, Hall's laboratory showed last year that a diet high in ultra-processed food led to overeating and weight gain in comparison to a minimally processed diet matched for carbs and fat. The plant-based, low-fat diet contained 10.3% fat and 75.2% carbohydrate, while the animal-based, low-carb diet was 10% carbohydrate and 75.8% fat. Both diets contained about 14% protein and were matched for total calories presented to the subjects, although the low-carb diet had twice as many calories per gram of food than the low-fat diet. On the low-fat menu, dinner might consist of a baked sweet potato, chickpeas, broccoli and oranges, while a low-carb dinner might be beef stir fry with cauliflower rice. Subjects could eat what and however much they chose of the meals they were given. "

Interestingly, our findings suggest benefits to both diets, at least in the short-term. While the low-fat, plant-based diet helps curb appetite, the animal-based, low-carb diet resulted in lower and more steady insulin and glucose levels," Hall said. "We don't yet know if these differences would be sustained over the long term." The researchers note that the study was not designed to make diet recommendations for weight loss, and results may have been different if participants were actively trying to lose weight. Further, all meals were prepared and provided for participants in an inpatient setting, which may make results difficult to repeat outside the lab, where factors such as food costs, food availability, and meal preparation constraints can make adherence to diets challenging. The tightly controlled clinical environment, however, ensured objective measurement of food intake and accuracy of data. 

 "To help us achieve good nutrition, rigorous science is critical ? and of particular importance now, in light of the COVID-19 pandemic, as we aim to identify strategies to help us stay healthy," said NIDDK Director Griffin P. Rodgers, M.D. "This study brings us closer to answering long-sought questions about how what we eat affects our health." 

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