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New discovery explains antihypertensive properties of green and black tea

Compounds in both green and black tea relax blood vessels by activating ion channel proteins in the blood vessel wall. The discovery helps explain the antihypertensive properties of tea and could lead to the design of new blood pressure-lowering medications.

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A new study from the University of California, Irvine shows that compounds in both green and black tea relax blood vessels by activating ion channel proteins in the blood vessel wall. The discovery helps explain the antihypertensive properties of tea and could lead to the design of new blood pressure-lowering medications.

Published in Cellular Physiology and Biochemistry, the discovery was made by the laboratory of Geoffrey Abbott, PhD, a professor in the Department of Physiology and Biophysics at the UCI School of Medicine. Kaitlyn Redford, a graduate student in the Abbott Lab, was first author of the study titled, “KCNQ5 potassium channel activation underlies vasodilation by tea.”

Results from the research revealed that two catechin-type flavonoid compounds (epicatechin gallate and epigallocatechin-3-gallate) found in tea, each activate a specific type of ion channel protein named KCNQ5, which allows potassium ions to diffuse out of cells to reduce cellular excitability. As KCNQ5 is found in the smooth muscle that lines blood vessels, its activation by tea catechins was also predicted to relax blood vessels – a prediction confirmed by collaborators at the University of Copenhagen.

“We found by using computer modeling and mutagenesis studies that specific catechins bind to the foot of the voltage sensor, which is the part of KCNQ5 that allows the channel to open in response to cellular excitation. This binding allows the channel to open much more easily and earlier in the cellular excitation process,” explained Abbott.

Because as many as one third of the world’s adult population have hypertension, and this condition is considered to be the number one modifiable risk factor for global cardiovascular disease and premature mortality, new approaches to treating hypertension have enormous potential to improve global public health. Prior studies demonstrated that consumption of green or black tea can reduce blood pressure by a small but consistent amount, and catechins were previously found to contribute to this property. Identification of KCNQ5 as a novel target for the hypertensive properties of tea catechins may facilitate medicinal chemistry optimization for improved potency or efficacy.

In addition to its role in controlling vascular tone, KCNQ5 is expressed in various parts of the brain, where it regulates electrical activity and signaling between neurons. Pathogenic KCNQ5 gene variants exist that impair its channel function and in doing so cause epileptic encephalopathy, a developmental disorder that is severely debilitating and causes frequent seizures. Because catechins can cross the blood-brain barrier, discovery of their ability to activate KCNQ5 may suggest a future mechanism to fix broken KCNQ5 channels to ameliorate brain excitability disorders stemming from their dysfunction.

Tea has been produced and consumed for more than 4,000 years and upwards of 2 billion cups of tea are currently drunk each day worldwide, second only to water in terms of the volume consumed by people globally. The three commonly consumed caffeinated teas (green, oolong, and black) are all produced from the leaves of the evergreen species Camellia sinensis, the differences arising from different degrees of fermentation during tea production.

Black tea is commonly mixed with milk before it is consumed in countries including the United Kingdom and the United States. The researchers in the present study found that when black tea was directly applied to cells containing the KCNQ5 channel, the addition of milk prevented the beneficial KCNQ5-activating effects of tea. However, according to Abbott, “We don’t believe this means one needs to avoid milk when drinking tea to take advantage of the beneficial properties of tea. We are confident that the environment in the human stomach will separate the catechins from the proteins and other molecules in milk that would otherwise block catechins’ beneficial effects.”

This hypothesis is borne out by other studies showing antihypertensive benefits of tea regardless of milk co-consumption. The team also found, using mass spectrometry, that warming green tea to 35 degrees Celsius alters its chemical composition in a way that renders it more effective at activating KCNQ5.

“Regardless of whether tea is consumed iced or hot, this temperature is achieved after tea is drunk, as human body temperature is about 37 degrees Celsius,” explained Abbott. “Thus, simply by drinking tea we activate its beneficial, antihypertensive properties.”

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Patients who are overweight or obese at risk of more severe COVID-19

COVID-19 patients with obesity were more likely to require oxygen and had a 73 per cent greater chance of needing invasive mechanical ventilation. Similar but more modest results were seen in overweight patients. No link was found between being overweight or obese and dying in hospital from COVID-19.

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Patients who are overweight or obese have more severe COVID-19 and are highly likely to require invasive respiratory support, according to a new international study.

The research, led by the Murdoch Children’s Research Institute (MCRI) and The University of Queensland and published in Diabetes Care, found obese or overweight patients are at high risk for having worse COVID-19 outcomes. They are also more likely to require oxygen and invasive mechanical ventilation compared to those with a healthy weight.

MCRI researcher Dr Danielle Longmore said the findings, which highlighted the relationship between obesity and increased COVID-19 disease burden, showed the need to urgently introduce strategies to address the complex socio-economic drivers of obesity, and public policy measures such as restrictions on junk food advertising.

“Although taking steps to address obesity in the short-term is unlikely to have an immediate impact in the COVID-19 pandemic, it will likely reduce the disease burden in future viral pandemics and reduce risks of complications like heart disease and stroke,” she said.

The study looked at hospitalised SARS-CoV-2 patients from 18 hospitals in 11 countries including China, America, Italy, South Africa and The Netherlands.

Among the 7244 patients aged 18 years and over, 34.8 per cent were overweight and 30.8 per cent were obese.

COVID-19 patients with obesity were more likely to require oxygen and had a 73 per cent greater chance of needing invasive mechanical ventilation. Similar but more modest results were seen in overweight patients. No link was found between being overweight or obese and dying in hospital from COVID-19.

Cardiovascular and pre-existing respiratory diseases were associated with increased odds of in-hospital deaths but not a greater risk for needing oxygen and mechanical ventilation. For patients with pre-existing diabetes, there was increased odds of needing invasive respiratory support, but no additionally increase in risk in those with obesity and diabetes.

Men were at an increased risk of severe COVID-19 outcomes and needing invasive mechanical ventilation. In those aged over 65 years, there was an increased chance of requiring oxygen and higher rates of in-hospital deaths.

The University of Queensland’s Dr Kirsty Short, who co-led the research, said almost 40 per cent of the global population was overweight or obese.

“Obesity is associated with numerous poor health outcomes, including increased risk of cardiometabolic and respiratory disease and more severe viral disease including influenza, dengue and SARS-CoV-1,” she said.

Dr Short said while previous reports indicated that obesity was an important risk factor in the severity of COVID-19, almost all this data had been collected from single sites and many regions were not represented. Moreover, there was a limited amount of evidence available about the effects of being overweight or obese on COVID-19 severity.

“Given the large scale of this study we have conclusively shown that being overweight or obese are independent risk factors for worse outcomes in adults hospitalised with COVID-19,” she said.

MCRI Professor David Burgner, who co-led the research, said the data would help inform immunisation prioritisation for higher-risk groups.

“At the moment, the World Health Organization has not had enough high-quality data to include being overweight or obese as a risk factor for severe COVID-19 disease. Our study should help inform decisions about which higher-risk groups should be vaccinated as a priority,” he said.

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Omega-3 supplements do double duty in protecting against stress

A high daily dose of an omega-3 supplement may help slow the effects of aging by suppressing damage and boosting protection at the cellular level during and after a stressful event, new research suggests.

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A high daily dose of an omega-3 supplement may help slow the effects of aging by suppressing damage and boosting protection at the cellular level during and after a stressful event, new research suggests.

Researchers at The Ohio State University found that daily supplements that contained 2.5 grams of omega-3 polyunsaturated fatty acids, the highest dose tested, were the best at helping the body resist the damaging effects of stress.

Compared to the placebo group, participants taking omega-3 supplements produced less of the stress hormone cortisol and lower levels of a pro-inflammatory protein during a stressful event in the lab. And while levels of protective compounds sharply declined in the placebo group after the stressor, there were no such decreases detected in people taking omega-3s.

The supplements contributed to what the researchers call stress resilience: reduction of harm during stress and, after acute stress, sustained anti-inflammatory activity and protection of cell components that shrink as a consequence of aging.

The potential anti-aging effects were considered particularly striking because they occurred in people who were healthy but also sedentary, overweight and middle-aged – all characteristics that could lead to a higher risk for accelerated aging.

“The findings suggest that omega-3 supplementation is one relatively simple change people could make that could have a positive effect at breaking the chain between stress and negative health effects,” said Annelise Madison, lead author of the paper and a graduate student in clinical psychology at Ohio State.

The research is published today (Monday, April 19, 2021) in the journal Molecular Psychiatry.

Madison works in the lab of Janice Kiecolt-Glaser, professor of psychiatry and psychology and director of the Institute for Behavioral Medicine Research at Ohio State. This paper is a secondary analysis of one of Kiecolt-Glaser’s earlier studies showing that omega-3 supplements altered a ratio of fatty acid consumption in a way that helped preserve tiny segments of DNA in white blood cells.

Those short fragments of DNA are called telomeres, which function as protective caps at the end of chromosomes. Telomeres’ tendency to shorten in many types of cells is associated with age-related diseases, especially heart disease, and early mortality.

In the initial study, researchers were monitoring changes to telomere length in white blood cells known as lymphocytes. For this new study, the researchers looked at how sudden stress affected a group of biological markers that included telomerase, an enzyme that rebuilds telomeres, because levels of the enzyme would react more quickly to stress than the length of telomeres themselves.

Specifically, they compared how moderate and high doses of omega-3s and a placebo influenced those markers during and after an experimental stressor. Study participants took either 2.5 grams or 1.25 grams of omega-3s each day, or a placebo containing a mix of oils representing a typical American’s daily intake.

After four months on the supplements, the 138 research participants, age 40-85, took a 20-minute test combining a speech and a math subtraction task that is known to reliably produce an inflammatory stress response.

Only the highest dose of omega-3s helped suppress damage during the stressful event when compared to the placebo group, lowering cortisol and a pro-inflammatory protein by an average of 19% and 33%, respectively.

Results from blood samples showed that both doses of omega-3s prevented any changes in telomerase levels or a protein that reduces inflammation in the two hours after participants experienced the acute stress, meaning any needed stress-related cell repair – including telomere restoration – could be performed as usual. In the placebo group, those repair mechanisms lost ground: Telomerase dropped by an average of 24% and the anti-inflammatory protein decreased by an average of at least 20%.

“You could consider an increase in cortisol and inflammation potential factors that would erode telomere length,” Madison said. “The assumption based on past work is that telomerase can help rebuild telomere length, and you want to have enough telomerase present to compensate for any stress-related damage.

“The fact that our results were dose-dependent, and we’re seeing more impact with the higher omega-3 dose, would suggest that this supports a causal relationship.”

The researchers also suggested that by lowering stress-related inflammation, omega-3s may help disrupt the connection between repeated stress and depressive symptoms. Previous research has suggested that people with a higher inflammatory reaction to a stressor in the lab may develop more depressive symptoms over time.

“Not everyone who is depressed has heightened inflammation – about a third do. This helps explain why omega-3 supplementation doesn’t always result in reduced depressive symptoms,” Kiecolt-Glaser said. “If you don’t have heightened inflammation, then omega-3s may not be particularly helpful. But for people with depression who do, our results suggest omega-3s would be more useful.”

The 2.5-gram dose of omega-3s is much higher than what most Americans consume on a daily basis, but study participants showed no signs of having problems with the supplements, Madison said.

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Heart patients advised to move more to avoid heart attacks and strokes

To prevent heart disease, European guidelines recommend at least 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity aerobic physical activity or an equivalent combination.

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Elevated blood pressure, high cholesterol and diabetes increase the risk of heart disease. But a large study today reveals that in people with these conditions, increasing activity levels is associated with a reduced likelihood of heart events and mortality. The research is presented at ESC Preventive Cardiology 2021, an online scientific congress of the European Society of Cardiology (ESC).

Study author Dr. Esmée Bakker of Radboud University Medical Center, Nijmegen, the Netherlands said: “Previous research showed that improvements in physical activity are beneficial to health. However, those studies were performed in the general population. In our study, we were interested to see if there were similar effects in individuals with cardiovascular risk factors such as high blood pressure, high cholesterol, and diabetes.”

The study included 88,320 individuals from the LifeLines Cohort Study. Participants underwent a physical examination and completed questionnaires about their medical history and lifestyle including exercise. The questionnaires were repeated after approximately four years.

Study participants were divided into five groups according to activity levels at baseline and four years: large reduction, moderate reduction, no change, moderate improvement, and large improvement. Participants were followed-up for a median of seven years after the first assessment for the occurrence of cardiovascular disease or death.

A total of 18,502 (21%) individuals had high blood pressure, high cholesterol, and/or diabetes at the start of the study. The average age of this group was 55 years. After adjusting for age, sex, and baseline physical activity, the researchers found that those with a moderate to large improvement in physical activity were around 30% less likely to develop cardiovascular disease or die during follow-up compared to those who did not change their activity level.

The remaining 69,808 (79%) participants did not have high blood pressure, high cholesterol, or diabetes at the start of the study. The average age of this group was 43 years. After adjusting for age, sex, and baseline physical activity, the researchers found that those with large reductions in physical activity had a 40% higher risk of cardiovascular disease or death compared to those who did not change their activity level.

Dr. Bakker said: “Our study suggests that to prevent heart attacks and strokes and boost longevity, healthy individuals should maintain their physical activity levels, while those with risk factors need to become more active. The associations we found were even more pronounced in people who were relatively sedentary at the start of the study, indicating that inactive people have the most to gain.”

To prevent heart disease, European guidelines recommend at least 150 minutes a week of moderate intensity or 75 minutes a week of vigorous intensity aerobic physical activity or an equivalent combination.

Dr. Bakker said: “If you are currently sedentary, walking is a good activity to start with. If you are already hitting the recommended amount, try doing 10 minutes more each day or increasing the intensity.”

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