The Gary Null Show

The Gary Null Show - 08.09.21

August 9, 2021

Cocoa flavanols contribute to faster oxygen uptake kinetics, improved blood flow

Liverpool Hope University, August 4, 2021

A bioactive compound found in cocoa powder and dark chocolate could help middle-aged adults enjoy exercise, a new study has suggested. The research analyzed the potential health benefits of cocoa flavanols, a plant nutrient extracted from cocoa beans.

Cocoa flavanols are found in abundance in cocoa powder, and to a lesser extent in dark chocolate, and can be consumed as a supplement. Because cocoa flavanols have a 'vasodilatory' effect, helping to increase blood flow, they've been shown to prevent blood clots and even combat memory decline. 

Now, a team of scientists from Liverpool Hope University and Liverpool John Moores University have tested the effects of cocoa flavanols when it comes to exercise in a group of sedentary adults aged between 40 and 60 years old.

And the report found that cocoa flavanols contribute to faster oxygen uptake kinetics—with improved blood flow the likely cause. 

Associate Professor Simon Marwood, subject lead in sport science at Liverpool Hope University, says the findings could be important when it comes to convincing people to get off the sofa and then stick with an exercise program. He said: "One barrier to starting an exercise plan is poor fitness in the first place, perhaps because of the discomfort associated with what might otherwise be light exercise. 

"Without frequent exercise, aging results in a slowing in the rate at which our oxygen consumption increases at the onset of exercise. This is due to impairments in the ability to supply blood to the exercising muscles at the onset of exercise.

"In previous studies, we have shown that this slowing of the rate of increase of oxygen consumption has a direct and inhibiting effect on the ability to tolerate exercise.

"The finding of faster increases in oxygen consumption at the onset of exercise with cocoa flavanols supplementation is therefore really encouraging for this age group since it suggests that a simple nutritional supplement can improve exercise tolerance, and therefore enhance the likelihood of sustaining an exercise program.

"This is a relatively small study but it's encouraging and has significant results, which could be the basis for further research."

Lead author Daniel Sadler, of Liverpool John Moores' School of Sport and Exercise Science, concludes: "These novel effects of cocoa flavanols in this demographic may contribute to improved tolerance of moderate-activity physical activities, which appear commonly present in daily life."

The research was published in the journal European Journal of Applied Physiology.

Professor Marwood says it's important to note that over-consumption of chocolate, dark or otherwise, isn't to be encouraged, although dark chocolate may contain cocoa flavanols. And the substance is most commonly available as a supplement, which is often used by amateur athletes to boost performance. 

The research itself focused on a group of healthy, middle-aged men and women with an average age of 45 years old and who typically engaged in less than two hours of structured exercise training per week.

Over a period of five weeks, prior to consuming the cocoa supplement, the group was put through a series of trials, using a lab-based exercise bike, where they were incrementally pushed to exhaustion. These trials were performed in order to establish a person's VO2 peak, the maximum amount of oxygen the body can use during exercise, as well as power output. 

The test subjects were then given either a daily 400 mg cocoa flavanol supplement or a placebo over the course of seven days. 

And at the end of that week, they got back on the cycle ergometers and took part in a series of step exercise tests, where they started pedaling at a baseline before the load was ramped up to either moderate or severe-intensity work rates.

The key measurement being analyzed was pulmonary VO2 kinetics, or τVO2, the time it takes for oxygen delivery to respond to the demands of exercise. 

The shorter the response time, the better equipped someone is to tolerate the given exercise. 

And what the research team discovered was that when the test subjects who'd consumed the cocoa flavanols were subjected to 'moderate' exercise, the VO2 kinetics time was 'significantly reduced' from around 40 seconds to 34 seconds. 

This reduction of six seconds is important, the team states, because it exceeds the minimum physiologically relevant change of around 5 seconds. 

The scientists add: "The reduction in τVO2 observed after cocoa flavanol supplementation in our middle-aged individuals reflects a shift toward values typically observed in younger healthy individuals."

And the report states: "Ultimately, the findings of the present study may have clinical potential in contributing to improved tolerance of daily life activity in middle-aged adults."

Flavonoids aren't just found in cocoa—they're also abundant in green tea, fruit and vegetables—and have anti-inflammatory as well as antioxidant properties. 

Liverpool John Moores' Daniel Sadler says you shouldn't rely on eating dark chocolate to get an effective dose of flavanols. 

He explains: "It is preferable to take supplements over eating dark chocolate since potential beneficial effects of cocoa flavanols occur during exercise when high doses are consumed—greater than 400 mg flavanols—and because dark chocolate contains fat and sugar that may negate the beneficial potential of any bioactive constituents."

In April this year, a separate study by researchers at the University of Birmingham found blood vessels were able to function better during mental stress when test subjects were given a cocoa drink containing high levels of flavanols compared to when drinking a non-flavanol enriched drink. 

The study, published in the journal Nutrients, could help to combat stress-induced ischemia while also paving the way for offering 'improved guidance to people about how to make the most of their dietary choices during stressful periods."



Vitamin D reduces the need for opioids in palliative cancer

Karolinska Institute (Sweden), August 4, 2021

Patients with vitamin D deficiency who received vitamin D supplements had a reduced need for pain relief and lower levels of fatigue in palliative cancer treatment, a randomized and placebo-controlled study by researchers at Karolinska Institutet shows. The study is published in the scientific journal Cancers.

Among patients with cancer in the palliative phase, vitamin D deficiency is common.

Previous studies have shown that low levels of vitamin D in the blood may be associated with pain, sensitivity to infection, fatigue, depression, and lower self-rated quality of life.

A previous smaller study, which was not randomized or placebo-controlled, suggested that vitamin D supplementation could reduce opioid doses, reduce antibiotic use, and improve the quality of life in patients with advanced cancer.

244 cancer patients with palliative cancer, enrolled in ASIH, (advanced medical home care), took part in the current study in Stockholm during the years 2017-2020.

Slower increase in opiod doses

All study participants had a vitamin D deficiency at the start of the study. They received either 12 weeks of treatment with vitamin D at a relatively high dose (4000 IE/day) or a placebo.

The researchers then measured the change in opioid doses (as a measurement of pain) at 0, 4, 8, and 12 weeks after the start of the study.

"The results showed that vitamin D treatment was well tolerated and that the vitamin D-treated patients had a significantly slower increase in opioid doses than the placebo group during the study period. In addition, they experienced less cancer-related fatigue compared to the placebo group," says Linda Björkhem-Bergman, senior physician at Stockholms Sjukhem and associate professor at the Department of Neurobiology, Healthcare Sciences, and Society, Karolinska Institutet.

Large study within ASIH

On the other hand, there was no difference between the groups in terms of self-rated quality of life or antibiotic use.

"The effects were quite small, but statistically significant and may have clinical significance for patients with vitamin D deficiency who have cancer in the palliative phase. This is the first time it has been shown that vitamin D treatment for palliative cancer patients can have an effect on both opioid-sensitive pain and fatigue," says first author of the study Maria Helde Frankling, senior physician at ASIH and postdoc at the Department of Neurobiology, Healthcare Science and Society, Karolinska Institutet.

The study is one of the largest drug studies conducted within ASIH in Sweden. One weakness of the study is the large drop-out rate. Only 150 out of 244 patients were able to complete the 12-week study because many patients died of their cancerduring the study.


Increasingly poor physical function from age 65 linked to increased risk of death

University of Paris (France), August 5, 2021

Increasing poor physical (motor) function from around age 65 is associated with an increased risk of death, finds research published by The BMJ today.

Signs of increasing decline, such as difficulty getting up from a chair or getting dressed, emerge up to 10 years before death, the findings show.

The researchers therefore suggest that early detection of changes in motor function “might offer opportunities for prevention and targeted interventions.”

It is well known that motor function, also commonly known as physical function or physical capability, declines with age, but rates of decline differ widely from person to person. And while studies show that decline in cognitive (mental) skills can emerge up to 15 years before death, it’s not clear whether the same is true for physical abilities.

To explore this further, researchers examined several measures of motor function for their associations with mortality over a 10 year period from around age 65.

Their findings are based on over 6,000 participants of the Whitehall II Study, which recruited participants aged 35-55 years in 1985-88 to look at the impact of social, behavioural, and biological factors on long term health. 

Between 2007 and 2016, participants underwent motor function assessments on up to three occasions. These included measures of walking speed, chair rise time, and grip strength, along with self-reported measures of functioning and difficulties with activities of daily living, such as dressing, using the toilet, cooking and grocery shopping.

Deaths from any cause were then recorded until October 2019.

After taking account of other potentially influential factors, the researchers found that poorer motor function was associated with an increased mortality risk of 22% for walking speed, 15% for grip strength and 14% for timed chair rises, while difficulties with activities of daily living were associated with a 30% increased risk.

These associations became progressively stronger with later life assessments.

Further analysis showed different patterns of change between participants who died and those who survived. 

For example, participants who died had poorer chair rise times than survivors up to 10 years before death, poorer self-reported functioning up to seven years before death, and more difficulties with activities of daily living up to four years before death. 

These differences increased steadily in the period leading to death.

This is an observational study, so can’t establish cause and the researchers point to some limitations, such as being unable to examine trajectories of motor function by cause of death or in specific minority groups, and not accounting for events such as falls or hospital admissions.

Nevertheless, they say this study “adds to the sparse literature on terminal decline in motor function and, to our knowledge, is the first to examine terminal and age related long term trajectories of multiple measures of motor function.”

The ageing of populations worldwide makes understanding of the functional status of older adults and change in functioning with age important, they write.

These results suggest that strategies to reduce accelerated decline should start before old age, and that early detection of changes in motor function might offer opportunities for prevention and targeted interventions, they conclude.

This study adds to a rapidly growing evidence base providing novel insights on healthy ageing, say researchers in a linked editorial.

They point out that as the study participants continue to age and more data becomes available, this will help to inform the development of interventions to promote healthy ageing. 

Although the authors suggest that “early detection of changes in motor function might offer opportunities for prevention and targeted interventions,” what these interventions would be and what specifically they would be aiming to achieve is unclear, they note. “Despite the focus on death as an outcome in these analyses, our goal should always be to add life to years, not just years to life.”


Researchers propose new treatment to prevent kidney stones – HCA in Garcinia Cambogia

University of Houston, August 8, 2021 


Researchers have found evidence that a natural fruit extract is capable of dissolving calcium oxalate crystals, the most common component of human kidney stones. This finding could lead to the first advance in the treatment of calcium oxalate stones in 30 years.


Jeffrey Rimer, associate professor of chemical engineering at the University of Houston, was lead author of the study, published Aug. 8 in the online edition of Nature. The work offers the first evidence that the compound hydroxycitrate (HCA) is an effective inhibitor of calcium oxalate crystal growth that, under certain conditions, is actually able to dissolve these crystals. Researchers also explain how it works.


The findings are the result of a combination of experimental studies, computational studies and human studies, Rimer said.


Kidney stones are small, hard mineral deposits that form inside the kidneys, affecting up to 12 percent of men and seven percent of women. High blood pressure, diabetes and obesity can increase the risk, and the reported incidence is on the rise.

Preventive treatment has not changed much over the last three decades. Doctors tell patients who are at risk of developing stones to drink lots of water and avoid foods rich in oxalate, such as rhubarb, okra, spinach and almonds. They often recommend taking citrate (CA), in the form of potassium citrate, a supplement that can slow crystal growth, but some people are unable to tolerate the side effects.


The project grew out of preliminary work done by collaborator John Asplin, a nephrologist at Litholink Corporation, who suggested HCA as a possible treatment. HCA is chemically similar to CA and is also available as a dietary supplement.

"HCA shows promise as a potential therapy to prevent kidney stones," the researchers wrote. "HCA may be preferred as a therapy over CA (potassium citrate)."


In addition to Rimer and Asplin, authors on the paper include Giannis Mpourmpakis and his graduate student, Michael G. Taylor, of the University of Pittsburgh; Ignacio Granja of Litholink Corporation, and Jihae Chung, a UH graduate student working in Rimer's lab.


The head-to-head studies of CA and HCA determined that while both compounds inhibit the growth of calcium oxalate crystals, HCA was more potent and displayed unique qualities that are advantageous for the development of new therapies.

The team of researchers then used atomic force microscopy, or AFM, to study interactions between the crystals, CA and HCA under realistic growth conditions. According to Rimer, the technique allowed them to record crystal growth in real time with near-molecular resolution.


Chung noted that the AFM images recorded the crystal actually shrinking when exposed to specific concentrations of HCA. Rimer suspected the initial finding was an abnormality, as it is rare to see a crystal actually dissolve in highly supersaturated growth solutions. The most effective inhibitors reported in the literature simply stop the crystal from growing.


It turned out that Chung's initial finding was correct. Once they confirmed it is possible to dissolve crystals in supersaturated solutions, researchers then looked at reasons to explain why that happened.


Mpourmpakis and Taylor applied density functional theory (DFT) - a highly accurate computational method used to study the structure and properties of materials - to address how HCA and CA bind to calcium and to calcium oxalate crystals. They discovered HCA formed a stronger bond with crystal surfaces, inducing a strain that is seemingly relieved by the release of calcium and oxalate, leading to crystal dissolution.


HCA was also tested in human subjects, as seven people took the supplement for three days, allowing researchers to determine that HCA is excreted through urine, a requirement for the supplement to work as a treatment.


While Rimer said the research established the groundwork to design an effective drug, questions remain. Long-term safety, dosage and additional human trials are needed, he said.


"But our initial findings are very promising," he said. "If it works in vivo, similar to our trials in the laboratory, HCA has the potential to reduce the incidence rate of people with chronic kidney stone disease."




Prolonged treatment with gotu kola improved memory, reduced amyloid beta pathology and activated antioxidant response pathway

Oregon Health & Science University, August 4, 2021

According to news reporting out of Portland, Oregon, research stated, “The medicinal herb Centella asiatica has been long been used for its neuroprotective and cognitive enhancing effects. We have previously shown that two weeks of treatment with a water extract of Centella asiatica (CAW) improves cognition and activates the endogenous antioxidant response pathway without altering amyloid-beta (A beta) plaque burden.”

Our news journalists obtained a quote from the research from Oregon Health & Science University (OHSU), “Here, we assess the effect of long-term treatment of CAW in the 5xFAD mouse model of A beta accumulation. Four-month-old 5xFAD mice were treated with CAW in their drinking water (2 g/L) for three months at which point they underwent cognitive testing as well as analysis of A beta plaque levels and antioxidant and synaptic gene expression. In order to confirm the involvement of the antioxidant regulatory transcription factor NRF2 on the effects of CAW on synaptic plasticity, neurons isolated from 5xFAD mice were also treated with CAW and the targeted inhibitor ML385. Three months of treatment with CAW improved spatial and contextual memory as well as executive function in 5xFAD mice. This improvement was accompanied by increased antioxidant gene expression and a decrease in A beta plaque burden relative to untreated 5xFAD animals. In isolated neurons, treatment with ML385 blocked the effects of CAW on dendritic arborization and synaptic gene expression. These results suggest that prolonged CAW exposure could be beneficial in Alzheimer’s disease and that these effects likely involve NRF2 activation.”

According to the news editors, the research concluded: “Moreover, these findings suggest that targeting NRF2 itself may be a relevant therapeutic strategy for improving synaptic plasticity and cognitive function in Alzheimer’s disease.”

This research has been peer-reviewed.



Resveratrol: The key to reducing elderly frailty?

Universidad Pablo de Olavide (Spain) , August 9, 2021

The so-called red wine nutrient resveratrol may help maintain muscle performance and reduce frailty in the elderly, research in mice has suggested. 

Using 48 young, mature and old mice models, the study found resveratrol improved muscle performance in the mature and old animals but not in the young. 

They found resveratrol – found in grapes, red wine, walnuts, peanuts and berries – “primed” the effect of exercise by increasing endurance, coordination and strength in the old animals as well as providing higher protection against oxidative damage and an increase in the mitochondrial mass responsible for the energy-generating process essential for cell metabolism. 

“Our results indicate that resveratrol can be considered an ergogenic compound that helps maintain muscle performance during ageing and subsequently reduces frailty and increases muscle performance in old individuals practising moderate exercise,” wrote the researchers from Universidad Pablo de Olavide in Seville, Spain and the Vietnam National University in Hanoi, Vietnam. 

Study details

Each experiment group animal was given a daily dose of about 500 μg of resveratrol for 4.5 months. After this period the mice were randomly divided again into sedentary and trained groups.

The trained mice were adapted to exercise then put on a rodent treadmill for 20 minutes per day, five days a week for six weeks.

The animals were then killed by cervical dislocation and the gastrocnemius muscle was quickly removed.

Old polyphenol, young results 

Discussing the results, lead author and professor at the Universidad Pablo de Olavide Dr Guillermo Lopez-Lluch told us while this was not the first time the polyphenol had been looked at within health ageing, this was the first time it had been associated with the improvement of muscle capacity in ageing.

Asked if the results meant older people should be recommended or even prescribed resveratrol, Professor Lopez-Lluch said: “The use of nutraceuticals such as resveratrol can be recommended in the case of poor diets lacking fresh vegetables rich in polyphenols.

“In aged people an unbalanced diet must be supplemented with extracts rich in these compounds accompanied by a more active life.”

In 2011 research in Italy estimated between 11–50% of over 80s suffer from age-related muscle loss sarcopenia, with the problem particularly prevalent in care homes. 

“Maintenance of muscle functionality is important to avoid frailty and to increase the independence and quality of life during ageing. It seems clear that for daily life activity, and hence a good quality of life, not only strength but also endurance is needed,” the researchers wrote in the British Journal of Nutrition

“Apart from the maintenance of a series of basic exercises, several nutritional bioactive compounds have been proposed to increase muscle function during ageing and to avoid sarcopenia.” 

The researchers said the "most controversial problem" with identifying effects of bioactive compounds was to find if the positive effects found in preclinical studies in animals produced the same response in humans.

"Regarding the effect of different polyphenols on physical capacity in humans, different clinical trials carried out to date have been unsuccessful or show controversial results and further studies are needed."

Yet Professor Lopez-Lluch said his research team did not have plans to study this effect of resveratrol in humans.

Instead they were currently awaiting funds to carry out a study about exercise, quality of nutrition and quality of life in elderly people.

“We hope this study will get a grant in the next months.”

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