Chronic inflammation causes a reduction in NAD+

Buck Institute research links hallmarks of aging: senescent cells activate CD38 which degrades NAD+, a key metabolite implicated in age-related decline

Buck Institute for Research on Aging, November 17, 2020

NAD+ (nicotinamide adenine dinucleotide), a key metabolite central to an efficient and healthy metabolism, declines with age. This previously unexplained phenomena is associated with numerous age-related diseases and has spawned the development of many nutritional supplements aimed at restoring NAD+ to more youthful levels. Publishing in Nature Metabolism, researchers at the Buck Institute have identified chronic inflammation as a driver of NAD+ decline. They show that an increasing burden of senescent cells, which is also implicated in the aging process, causes the degradation of NAD via the activation of CD38 (cyclic ADP ribose hydrolase) a protein that is found on the cell membranes both inside and on the surface of many immune cells.

“We are very excited to link two phenomena which have been separately associated with aging and age-related disease,” said Eric Verdin, MD, Buck Institute President and CEO and senior author of the paper. “The fact that NAD+ decline and chronic inflammation are intertwined provides a more holistic, systemic approach to aging and the discovery of CD38 macrophages as the mediator of the link between the two gives us a new target for therapeutic interventions.”

The faucet or the sink? Or both?

Scientists have been aware that NAD+ levels decrease with age but Verdin says what hasn’t been clear is whether the decline stems from decreased production of NAD+, a problem with the “faucet,” or from its degradation, an issue akin to a “leaky sink”. “Our data suggests that, at least in some cases, the issue stems from the leaky sink,” he said, “Ultimately I think supplementation will be part of the equation, but filling the sink without dealing with the leak will be insufficient to address the problem.” Verdin says preliminary data suggests that blocking CD38 activity in older animals restores NAD+ levels in specific tissues.

Unique Buck collaboration drives the research

The research, led by Anthony J. Covarrubias, PhD, a postdoctoral fellow in the Verdin lab, also involved Buck professor Judith Campisi and her laboratory, which is recognized internationally for pioneering work in the field of cellular senescence. Experiments were done in mice and involved metabolic tissue from visceral white fat and the liver which were examined during aging and acute responses to inflammation. The work was validated in primary human macrophages. “Our initial hypothesis was that CD38 activation would be driven by inflammation,” Covarrubias said, “But we found that in this case, the activation occurred with both acute and age-related inflammation. That was a surprise.”

Inflammaging: Cellular senescence and the SASP

Senescent cells, which stop dividing in response to DNA damage, spew a multitude of pro-inflammatory proteins, called the senescence-associated secretory phenotype or SASP. Evolution selected cellular senescence as a protective measure against cancer; but as senescent cells accumulate in tissues over the course of a lifetime, the SASP drives low grade chronic inflammation which is associated with age-related disease, including late life cancer. “These inflammatory proteins in the SASP induce macrophages to proliferate, express CD38 and degrade NAD+. It’s a maladaptive process,” said Covarrubias, “But drugs that target the SASP or CD38 may offer us another way to deal with the decline of NAD+.”

NAD: Essential for life

NAD+ is found in every cell; it promotes cellular energy production and supports cellular metabolism. NAD is also critical for the activity of sirtuins which have global anti-aging properties. Comparing our cellular metabolism to a cash economy, Verdin describes NAD+ as the armored trucks that transfer money between institutions. “Money is the fuel. If you can’t transport the money, then the whole economy comes to a halt. It all comes crashing down. That’s how important NAD+ is to our cellular health and we look forward to applying this discovery to our efforts to stem the ravages of age-related disease.”

Grape seed proanthocyanidin extract promotes skeletal muscle fiber transformation which supports increased fatigue resistance

Sichuan Agricultural University (China), November 16, 2020

According to news reporting originating from Sichuan, People’s Republic of China, by NewsRx correspondents, research stated, “Transformation of skeletal muscle fiber type from fast twitch to slow twitch has significances for sustained contractile and stretchable events, energy homeostasis and antifatigue ability. However, the regulation of skeletal muscle fiber type transformation through nutritional intervention is still not fully spelled out.”

Our news editors obtained a quote from the research from Sichuan Agricultural University, “Grape seed proanthocyanidin extract (GSPE) has been widely reported to play a broader role in many aspects of diseases with its various pharmacological and health-promoting effects. In this study, we found that GSPE significantly improved the fatigue resistance in mice. GSPE up-regulated slow myosin heavy chain (MyHC) and down-regulated fast MyHC, accompanied by increases in activities of succinic dehydrogenase and malate dehydrogenase and by decreased lactate dehydrogenase activity in muscle of mice and in C2C12 myotubes. The AMP-activated protein kinase (AMPK) signaling can be activated by GSPE. Several upstream and downstream factors of AMPK signaling such as liver kinase B1, nuclear respiratory factor 1, calcium calmodulin-dependent protein kinase kinase beta, sirtuin1 and peroxisome proliferator activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) were also up-regulated by GSPE. Specific inhibition of AMPK signaling by AMPK inhibitor compound C or by AMPK alpha 1 siRNA significantly abolished the GSPE-induced the activation of AMPK and the increase of PGC-1 alpha, and attenuated the GSPE-induced increase of slow MyHC and decrease of fast MyHC in C2C12 myotubes.”

According to the news editors, the research concluded: “Taken together, we revealed that GSPE promotes skeletal muscle fiber type transformation from fast twitch to slow twitch through AMPK signaling pathway, and this GSPE-induced fiber type transformation may contribute to increased fatigue resistance.”

This research has been peer-reviewed.

Complementary, Alternative Medicine Use Increasing for MS

Oregon Health & Science University, November 6, 2020

For people with multiple sclerosis (pwMS), there has been an increase in use of complementary and alternative medicine (CAM), according to a study published in the June issue of Multiple Sclerosis and Related Disorders.

Elizabeth Silbermann, MD, from the Oregon Health & Science University in Portland, and colleagues administered a survey in Oregon and Southwest Washington in 2018 to describe updated patterns of CAM use in pwMS and compare trends with those from a survey conducted in 2001.

The researchers found that in 2018, to treat their MS, 81% of the respondents used a CAM supplement(vitamins, minerals, or herbs), 39% used mind-body therapies, 41% used a specific diet, and 81% used exercise. There were increases in the use of supplements (65 to 81%), exercise (67 to 81%), and mind-body therapies (14 to 39%). There was also a ninefold increase in the likelihood of participants speaking to their neurologists about CAM use (6.7 to 55.4%). In 2018, female sex, progressive disease, and longer time since diagnosis of MS were factors associated with CAM use.

“CAM use overall has increased and pwMS are communicating more with their MS providers about their CAM use,” the authors write. “Both pwMS and providers need high-quality evidence-based research to guide appropriate education regarding both safety and efficacy when CAM is in the MS treatment strategy.”

How Exercise Might Affect Immunity to Lower Cancer Risk

Working out may enhance the immune system’s ability to target and eradicate cancer cells, a study in mice suggests

Karolinska Institute (Sweden), University of Padova (Italy), Cambridge University, November 13, 2020

Exercise may help to fight cancer by changing the inner workings of certain immune cells, according to an important new study in mice of how running affects tumors. The study involved rodents but could also have implications for understanding how exercise might affect cancer in people as well.

We already have considerable and compelling evidence that exercise alters our risks of developing or dying from malignancies. In a large-scale 2016 epidemiological study, for instance, highly active people were found to be much less likely to develop 13 different types of cancer than people who rarely moved.

Likewise, a review of past research released last year by the American College of Sports Medicine concluded that regular exercise may reduce our risks of developing some cancers by as much as 69 percent. That analysis also found that exercise may improve treatment outcomes and prolong life in people who already have cancer.

But it is not yet fully clear how working out may affect tumors. Animal studies show that exercise lessens inflammation and may otherwise make the body’s internal environment less hospitable to malignancies. But fundamental questions remain unanswered about the interplay of exercise and cancer.

So, recently, a group of scientists from the Karolinska Institute in Stockholm and other institutions began to wonder about white blood cells. Part of the immune system, white blood cells play a key role in our defense against cancer by noting, navigating to and often annihilating malignant cells. Researchers have known for some time that different types of immune cells tend to target different types of cancer. But little has been known about if and how exercise affects any of these immune cells and if those changes might somehow be contributing to exercise’s cancer-blunting effects.

Now, for the new study, which was published in October in eLife, the scientists in Sweden decided to learn more by inoculating mice with different types of cancer cells and letting some of the rodents run, while others remained sedentary. After several weeks, the researchers saw that some of the runners showed little evidence of tumor growth. More intriguing, most of these active mice had been inoculated with cancer cells that are known to be particularly vulnerable to a specific type of immune cell, known as CD8+ T cells, which tend, primarily, to fight certain forms of breast cancer and other solid tumors.

Perhaps, the researchers speculated, exercise was having particular impacts on those immune cells.

To find out, they then chemically blocked the action of these T cells in animals carrying tumor cells and let them run. After several weeks and despite being active, the animals without functioning CD8+ T cells showed significant tumor growth, suggesting that the CD8+ cells, when working, must be a key part of how exercise helps to stave off some cancers.

For further confirmation, the scientists then isolated CD8+ T cells from animals that had run and those that had not. They then injected one or the other type of T cells into sedentary, cancer-prone animals. Animals that received immune cells from the runners subsequently fought off tumors noticeably better than animals that had received immune cells from inactive mice.

These results surprised and excited the researchers, says Randall Johnson, a professor of molecular physiology with dual appointments at the University of Cambridge in England and the Karolinska Institute, who oversaw the new study. They seemed to demonstrate “that the effect of exercise on the T cells is intrinsic to the cells themselves and is persistent,” he says.

In other words, exercise had changed the cells in ways that lasted.

But what, the scientists wondered, was exercise doing to the cells that made them extra effective at fighting tumors? To explore that question, the researchers let some mice run until they tired themselves out, while others sat quietly. They then drew blood from both groups and put the samples through a sophisticated machine that notes and counts all of the molecules there.

The blood samples turned out to be quite different at a molecular level. The runners’ blood contained far more substances related to fueling and metabolism, with especially high levels of lactate, which is produced in abundance by working muscles. Perhaps, the scientists speculated, lactate was affecting the runners’ T cells?

So, they added lactate to CD8+ T cells isolated from mice and grown in dishes and found that these cells became more active when faced with cancer cells than other T cells. Basically, having marinated in lactate, they became better cancer fighters.

In simpler terms, Dr. Johnson says, “It does seem from our studies that these T cells are potently affected by exercise.”

Of course, his and his colleagues’ experiments involved mice, not people. We humans also produce extra lactate and other related molecules after exercise (which the researchers confirmed in a final portion of their study, by drawing blood from people after a run and analyzing its molecular composition). But whether our CD8+ T cells respond in precisely the same way to working out remains uncertain.

The study also does not show if all exercise has the same effects on T cells or whether some workouts might be more beneficial than others for amping up these cells’ powers. It also does not suggest that exercise reduces cancer risk and progression solely by strengthening these cells. More likely, being active affects how well our bodies deal with malignancies in multiple and perhaps interlinked ways

Green spaces keep hearts healthy and save lives

University of Miami School of Medicine, November 16th, 2020

Planting trees and creating urban parks brings more green spaces and cleaner air, cutting heart deaths and saving lives.

LONDON, 16 November, 2020 − A vast study of the incidence of heart disease, the amount of green spaces and air quality in each county of the United States has shown that the presence of trees, shrubs and grass saves lives.

It has long been known that particulate matter from industry and car exhausts is bad for lungs and hearts. While it is also accepted that the greenery absorbs pollution, it has been hard until now to relate the extent of the two effects.

Using the data collected by NASA from satellites to calculate the greenness of vast areas of the US, the researchers compared it with the national death rates from the Atlas of Heart Disease.

They overlaid this with data from the Environment Protection Agency’s air quality measurements of particulate matter for each county and the Census Bureau’s information on age, race, education and income by county.

Using an internationally recognised system to measure the amount of green vegetation in any location, from a barren area of rock at one extreme (0.00 on the scale) to dense tropical rain forest (0.80) at the other, they found a measurable link between greenness and survival rates.

Policy shift needed

For every 0.10 (12.5%) increase in what’s called the Normalised Difference Vegetation Index, heart disease decreased by 13 deaths per 100,000. For every one microgram increase in particulate matter per cubic metre of air, heart disease increased by roughly 39 deaths per 100,000.

“We found that areas with better air quality have higher greenness, and that having higher greenness measures, in turn, is related to having a lower rate of deaths from heart disease,” said William Aitken, a cardiology fellow with the University of Miami Miller School of Medicine, Florida.

“Given the potential cardiovascular benefits of higher greenness measures, it’s important that dialogue about improved health and quality of life include environmental policies that support increasing greenness,” he said.

The research is significant in the battle against climate change too. Asian countries, particularly India and China, have severe problems with early death and disease as a result of air pollution. They have concentrated their efforts for reducing air pollution by reducing traffic and suppressing coal burning.

It is clear from this research that they could both remove particulates from the air and reduce the amount of carbon dioxide in the atmosphere by increasing the amount of vegetation in polluted areas.

The US researchers hope their results will encourage clinical trials using built environment interventions (e.g., tree planting to increase the presence of vegetation) to improve cardiovascular health. “We will be performing a longitudinal study in Miami to assess if changes in neighbourhood greenness over time are associated with changes in cardiovascular disease,” Dr. Aitken said.

Commenting on the research Joel Kaufman, a volunteer expert for the American Heart Association and a professor of environmental and occupational health at the University of Washington, Seattle, said in addition to the actions that individuals could take to ensure healthy lives, such as not smoking, being physically active and controlling cholesterol, environmental factors had turned out to be very important.

Ambient air pollution from burning fossil fuels is one of the major factors. Research over 20 years has shown that living in areas with higher concentrations of air pollutants, and breathing in the pollution, leads to higher rates of cardiovascular disease. Demonstrably, green spaces matter.

Dr Kaufman said that community-led action had mostly been directed at increasing controls over the sources of air pollution affecting the environment. But another effective approach would be to increase the level of greenness, planting trees, shrubs and grass.

In a statement the American Heart Association said long-term exposure to air pollution reduced life expectancy by between several months and a few years, depending on its severity. Cutting pollution improved the health and life expectancy of those living in the area quite quickly.

Coenzyme Q10 supplementation associated with improved antioxidant status, glycemic control

Fu Jen Catholic University (Taiwan), November 16 2020.

The September 2020 issue of the journal Antioxidants published the results of a study that found improvements in antioxidant status and aspects of glucose control in well-trained college athletes who supplemented with high dose coenzyme Q10 (CoQ10), an antioxidant used by nearly every cell of the body in the production of energy.

Taiwanese researchers enrolled 31 men and women who were required to train for over 12 hours each week. Seventeen participants received 300 milligrams of the ubiquinone form of CoQ10 and the remainder received a placebo for a 12-week period. Body mass index, blood pressure, plasma and white blood cell levels of CoQ10, plasma and red blood cell levels of malondialdehyde (MDA, a marker of oxidative stress), total antioxidant capacity, hemoglobin A1c (HbA1c, a marker of long term glucose control) and other factors were assessed before and after the treatment period.

At the study’s conclusion, plasma CoQ10 levels were significantly higher and red blood cell MDA levels were significantly lower in comparison with the placebo group (which experienced a significant increase in MDA). Higher white blood cell CoQ10 levels were associated with reductions in hemoglobin A1c and insulin resistance and improvement in the participants’ quantitative insulin sensitivity check index (QUICKI). Higher total antioxidant capacity levels were associated with improved insulin sensitivity.

The current investigation “is the first study to clarify the causal relationship between ubiquinone status and antioxidant capacity and glycemic control after ubiquinone supplementation,” Chien-Chang Ho of Fu Jen Catholic University in New Taipei City, Taiwan and colleagues announced.

“Athletes may develop high oxidative stress from exercise training. In the present study, we found that ubiquinone supplementation may yield an increase of ubiquinone status and further increase antioxidant capacity, which benefits glycemic control in athletes,” they concluded.

Carnitine supplementation associated with improvement of metabolic syndrome

Sungshin Women’s University (S Korea), November 17, 2020

A review and meta-analysis of randomized, placebo-controlled trials published on September 12, 2020 in the journal Nutrients found improvement in factors that characterize metabolic syndrome (MetSyn) among men and women given L-carnitine supplements.

Metabolic syndrome is determined by the presence of three or more factors that include high blood pressure, elevated fasting triglycerides, low levels of high density lipoprotein (HDL) cholesterol, increased abdominal circumference and high fasting blood glucose. The presence of metabolic syndrome is associated with an increased risk of developing type 2 diabetes and cardiovascular disease.

“This study is the first to investigate the effect of L-carnitine supplementation on the biomarkers of MetSyn,” authors Munji Choi of Sungshin Women’s University and colleagues announced.

Dr Choi and associates selected nine articles that reported the findings of trials that evaluated the effects of L-carnitine supplementation among 508 participants and reported data concerning fasting blood glucose, triglycerides, waist circumference, blood pressure or HDL cholesterol. L-carnitine doses ranged from 0.75 milligrams (mg) to 3 grams per day.

Supplementing with L-carnitine was associated with significant reductions in waist circumference and systolic blood pressure in comparison with the placebo groups. When studies that tested doses of 1 to 3 grams were analyzed, L-carnitine was additionally associated with a significant decrease in fasting blood glucose and triglycerides and an increase in beneficial HDL cholesterol. “Ultimately, 2–3 g/day of supplemented L-carnitine is recommended,” the authors remarked.

“L-carnitine supplementation is correlated with a significant reduction in waist circumference and blood pressure,” they concluded. “Additionally, L-carnitine supplementation at a dose of 1–3 gram/day could improve MetSyn by reducing fasting blood sugar and triglycerides and increasing HDL cholesterol.”

Chemicals in your living room cause diabetes

University of California at Riverside, November 10, 2020

A new UC Riverside study shows flame retardants found in nearly every American home cause mice to give birth to offspring that become diabetic.

These flame retardants, called PBDEs, have been associated with diabetes in adult humans. This study demonstrates that PBDEs cause diabetes in mice only exposed to the chemical through their mothers.

“The mice received PBDEs from their mothers while they were in the womb and as young babies through mother’s milk,” said Elena Kozlova, lead study author and UC Riverside neuroscience doctoral student. “Remarkably, in adulthood, long after the exposure to the chemicals, the female offspring developed diabetes.”

Results of the study have been published in the journal Scientific Reports.

PBDEs are common household chemicals added to furniture, upholstery, and electronics to prevent fires. They get released into the air people breathe at home, in their cars, and in airplanes because their chemical bond to surfaces is weak.

“PBDEs are everywhere in the home. They’re impossible to completely avoid,” said UCR neuroscientist and corresponding author of the study, Dr. Margarita Curras-Collazo.

“Even though the most harmful PBDEs have been banned from production and import into the U.S., inadequate recycling of products that contain them has continued to leach PBDEs into water, soil, and air. As a result, researchers continue to find them in human blood, fat, fetal tissues, as well as maternal breast milk in countries worldwide.”

Given their previous association with diabetes in adult men and women, and in pregnant women, Curras-Collazo and her team wanted to understand whether these chemicals could have harmful effects on children of PBDE-exposed mothers. But such experiments can only be done on mice.

Diabetes leads to elevated levels of blood glucose, or blood sugar. After a meal, the pancreas releases insulin, a hormone that helps cells utilize glucose sugar from food. When cells are resistant to insulin, it doesn’t work as intended, and levels of glucose remain high in the blood even when no food has been eaten.

Chronically high levels of glucose can cause damage to the eyes, kidneys, heart, and nerves. It can also lead to life-threatening conditions.

“This study is unique because we tested both the mothers and their offspring for all the hallmarks of diabetes exhibited in humans,” Curras-Collazo said. “This kind of testing has not been done before, especially on female offspring.”

The researchers gave PBDEs to the mouse mothers at low levels comparable to average human environmental exposure both during pregnancy and lactation.

All of the babies developed glucose intolerance, high fasting glucose levels, insulin insensitivity, and low blood insulin levels, which are all hallmarks of diabetes. In addition, researchers also found the babies had high levels of endocannabinoids in the liver, which are molecules associated with appetite, metabolism, and obesity.

Though the mothers developed some glucose intolerance, they weren’t as affected as their offspring.

“Our findings indicate that chemicals in the environment, like PBDEs, can be transferred from mother to offspring, and exposure to them during the early developmental period is damaging to health,” Curras-Collazo said.

The research team feels future longitudinal studies in humans are needed to determine the long-term consequences of early-life PBDE exposure.

“We need to know if human babies exposed to PBDEs both before and after birth go on to become diabetic children and adults,” Kozlova said.

In the meantime, Curras-Collazo advises people to limit PBDE exposure by taking steps such as washing hands before eating, vacuuming frequently, and buying furniture and other products that do not contain it. She also hopes expectant mothers are well informed about stealth environmental chemicals that can affect their unborn and developing children, as well as their breast milk.

“We believe the benefits babies get from mothers’ milk far outweigh the risks of passing on the PBDEs to children. We do not recommend curtailing breastfeeding,” she said. “But let’s advocate for protecting breast milk and our bodies from killer couch chemicals.”

How pomegranate extract alters breast cancer stem cell properties

University at Albany, November 9, 2020

A University at Albany research team has found evidence suggesting that the same antioxidant that gives pomegranate fruit their vibrant red color can alter the characteristics of breast cancer stem cells, showing the superfood’s potential for aiding in much more than diabetes or heart disease as previously thought.

Pomegranate extract, derived mainly from the skin of the fruit, is known for having high levels of powerful antioxidants called polyphenols. Professor Ramune Reliene, associate professor of Environmental Health Sciences in the School of Public Health, and graduate assistant Sameera Nallanthighal, both working with UAlbany’s Cancer Research Center, wondered if these antioxidants could demonstrate cancer-fighting effects.

Because not all cancer cells are the same and tumors are comprised of many cell types, they decided to target the one long thought to be the most dangerous in any given tumor: cancer stem cells.

The Cells

Stem cells are unlike other types of cells in that they have a remarkable ability to self-divide and reproduce themselves, even giving rise to other types of cells. This self-dividing nature alone is not dangerous; in fact, normal tissue stem cells can replace dying cells and even repair damaged tissue.

The danger arises if stem cells become cancer stem cells, because their division and renewing ability carries over to cancer progression by aiding in tumor initiation, growth, and even re-initiating cancerous tumors long after a person has been declared cancer-free. Compounding these issues are the fact that cancer stem cells are thought to be more resistant to therapy than other types of cancer cells.

As such, cancer stem cells have become an important target in cancer therapy and prevention more so than other cancer cells, because of the idea that if the stem cells can be slowed or made “less stem-like,” the cancer itself could be slowed too.

The Study

Together with an undergraduate student researcher Kristine Elmaliki, Reliene and Nallanthighal conducted experiments using cancer cells lines that are the prototypes of breast cancer stem cells. These cells, which display the exact properties of cancer stem cells, were treated with diluted pomegranate extract and incubated for periods ranging from one to six days.

During this time, the team measured several markers of breast cancer stem cells in both the pomegranate extract treated cells and untreated cells. They then compared the results between the groups and observed significant differences between the cancer stem cell prototypes that were treated with pomegranate extract.

Additionally, the cells that were treated with pomegranate extract were treated with relatively small amounts – thought to be manageable for a person to consume by simply purchasing the product at a grocery store and incorporating it into their diet.

“One thing we found surprising is that relatively low concentrations of the extract are able to modify the ability of cancer stem cells to reproduce themselves,” said Reliene.

The Findings

Reliene, Nallanthighal and Elmaliki made several notable findings, including:
Pomegranate extract inhibits breast cancer cells ability to self-renew
The inhibitory effect is maintained for several cell generations of newly formed cells (the equivalent to children and grandchildren of pomegranate extract-exposed parent cells) that have never been exposed to pomegranate extract but still have difficulties in self-renewing
Pomegranate extract converts cancer stem cells to cells that look like more traditional cancer cells and which may successfully be eliminated by cancer drugs.

“Our evidence alone does not suggest that pomegranate is the end-all-be-all-cure of breast cancer, but pomegranate extract shows promising potential for having a positive effect in both the primary cancer prevention and inhibition of the disease progression,” said Reliene. “It warrants further investigation of its overall possibilities,” she continued.

Calcium supplementation may be needed in addition to vitamin D to lower fracture risk

King Chulalongkorn Memorial Hospital (Thailand), November 10, 2020

According to news reporting originating from Bangkok, Thailand, research stated, “Vitamin D supplement is one of the current possible interventions to reduce fall and fracture. Despite having several studies on vitamin D supplement and fall and fracture reductions, the results are still inconclusive.”

Our news editors obtained a quote from the research from King Chulalongkorn Memorial Hospital, “We conducted a meta-analysis to examine the effect of vitamin D supplement in different forms and patient settings on fall and fracture. A systematic literature research was conducted in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) to compare the effects of vitamin D supplements on fall and fracture outcomes. Random-effect models were used to compute the weighted mean difference for continuous variables and the risk ratio for binary variables. Forty-seven RCTs with 58,424 participants were identified reporting on fall outcome. Twenty-four of 47 studies with 40,102 subjects also reported fracture outcome. Major populations were elderly women with age less than 80 years. Overall, vitamin D supplement demonstrated a significant effect on fall reduction, RR = 0.948 (95% CI 0.914-0.984;P = .004, I-2 = 41.52). By subgroup analyses, only vitamin D with calcium supplement significantly reduce fall incidence, RR = 0.881 (95% CI 0.821-0.945;P < .001, I-2 = 49.19). Vitamin D3 supplement decreased incidence of fall but this occurred only when vitamin D3 was supplemented with calcium. Regarding fracture outcome, vitamin D supplement failed to show fracture lowering benefit, RR = 0.949 (95% CI 0.846-1.064;P = .37, I-2 = 37.92). Vitamin D along with calcium supplement could significantly lower fracture rates, RR = 0.859 (95% CI 0.741-0.996;P = .045, I-2 = 25.48). The use of vitamin D supplement, especially vitamin D3 could reduce incidence of fall.”

According to the news editors, the research concluded: “Only vitamin D with calcium supplement showed benefit in fracture reduction.

Low levels of choline in pregnant Black American women associated with higher levels of stress

University of Colorado, November 17, 2020

(November 16, 2020) – Researchers at the University of Colorado Anschutz Medical Campus have found that many pregnant Black Americans have low levels of choline, an essential nutrient that aids in prenatal brain development. Stress caused by institutional racism may play a role.

The study, out now in Schizophrenia Bulletin, also found that these low levels of choline were associated with higher levels of the stress hormone cortisol. Higher cortisol induces the mother to hold choline in her liver instead of delivering it to the baby.

“One of the possible causes of higher cortisol and lower choline levels in Black American women is the burden of institutional racism and the chronic subconscious stress that it causes,” said Robert Freedman, MD, professor of psychiatry at the CU Anschutz Medical Campus and the study’s lead researcher.

Women with lower levels of choline delivered on average two weeks prematurely, putting the babies at an increased risk of attention deficit disorder and other childhood mental health problems.

Researchers surveyed a sample of 183 pregnant women, with 25 self-identified Black women.

Choline levels in Black women were lower than those of white women from the same neighborhoods. While Black participants did not indicate more stress, their hair cortisol levels were markedly higher.

Researchers also examined a group of pregnant Black women in Uganda. Choline levels obtained from those 166 participants were significantly higher than Black American levels, indicating that high stress rather than ancestry contributes to low choline levels in Black American women.

In a separate clinical trial with 100 pregnant women, 50 women, of whom seven were Black, received a phosphatidylcholine supplement to raise their choline levels. Fifty received a placebo, eight of them were Black.

Both groups received instruction on how to increase choline in their diets. Premature birth was prevented in the seven Black women who received choline supplements, but not in the eight who received placebo. By age four, their children had fewer problems with attention and social behavior with others.

These two studies combined represent the largest group of Black women studied for the effects of prenatal choline on the outcome of their pregnancy.

“We hope to get the word out, to all women and especially to stressed, pregnant Black women, that taking supplemental choline, in addition to the prenatal vitamins they already take, can significantly improve outcomes for their children,” said Freedman.

Chronic inflammation causes a reduction in NAD+

Buck Institute research links hallmarks of aging: senescent cells activate CD38 which degrades NAD+, a key metabolite implicated in age-related decline

Buck Institute for Research on Aging, November 17, 2020

The faucet or the sink? Or both?

Unique Buck collaboration drives the research

Inflammaging: Cellular senescence and the SASP

NAD: Essential for life

Grape seed proanthocyanidin extract promotes skeletal muscle fiber transformation which supports increased fatigue resistance

Sichuan Agricultural University (China), November 16, 2020

This research has been peer-reviewed.

Go (over) easy on the eggs: ‘Egg-cess’ consumption linked to diabetes

University of South Australia, China Medical University, Qatar University, November 15, 2020

Scrambled, poached or boiled, eggs are a popular breakfast food the world over. Yet the health benefits of the humble egg might not be all they’re cracked up to be as new research from the University of South Australia shows that excess egg consumption can increase your risk of diabetes.

Conducted in partnership with the China Medical University, and Qatar University, the longitudinal study (1991 to 2009) is the first to assess egg consumption in a large sample of Chinese adults.

It found that people who regularly consumed one or more eggs per day (equivalent to 50 grams) increased their risk of diabetes by 60 per cent.

With the prevalence of diabetes in China now exceeding 11 per cent – above that of the global average of 8.5 per cent – diabetes has become a serious public health concern.

The economic impact of diabetes is also significant, accounting for 10 per cent of global health expenditure (USD $760 billion). In China, diabetes-related costs have exceeded USD $109 billion.

Epidemiologist and public health expert, UniSA’s Dr Ming Li, says the rise of diabetes is a growing concern, especially in China where changes to the traditional Chinese diet are impacting health.

“Diet is a known and modifiable factor that contributes to the onset Type 2 diabetes, so understanding the range of dietary factors that might impact the growing prevalence of the disease is important,” Dr Li says.

“Over the past few decades China has undergone a substantial nutritional transition that’s seen many people move away from a traditional diet comprising grains and vegetables, to a more processed diet that includes greater amounts of meat, snacks and energy-dense food.

“At the same time, egg consumption has also been steadily increasing; from 1991 to 2009, the number of people eating eggs in China nearly doubled*.

“While the association between eating eggs and diabetes is often debated, this study has aimed to assess people’s long-term egg consumption of eggs and their risk of developing diabetes, as determined by fasting blood glucose.

“What we discovered was that higher long-term egg consumption (greater than 38 grams per day) increased the risk of diabetes among Chinese adults by approximately 25 per cent.

“Furthermore, adults who regularly ate a lot of eggs (over 50 grams, or equivalent to one egg, per day) had an increased risk of diabetes by 60 per cent.”

The effect was also more pronounced in women than in men.

Dr Li says that while these results suggest that higher egg consumption is positively associated with the risk of diabetes in Chinese adults, more research is needed to explore causal relationships.

“To beat diabetes, a multi-faceted approach is needed that not only encompasses research, but also a clear set of guidelines to help inform and guide the public. This study is one step towards that long-term goal.”

Veganism: Vitamin B12 is well supplemented, iodine is a matter of concern

A study shows differences between vegan and mixed diets

German Federal Institute for Risk Assessment, November 9, 2020

There was no significant difference with regard to vitamin B12, which was present in approximately the same amount in the blood of both groups. Since vitamin B12 is taken up almost exclusively by animal food, the supply of participants following a vegan diet could be due to the intake via dietary supplements. “This study makes it possible to compare a vegan diet with a mixed diet with regard to a variety vitamins and trace elements,” says BfR President Professor Dr. Dr. Andreas Hensel. “Both diets investigated revealed a lack of iodine. However, the shortage is clearly more distinct in the vegan variant.”

In the RBVD study, the BfR research team analysed blood and urine samples and evaluated lifestyle questionnaires and dietary protocols. Of those participating (18 women and men respectively per group aged 30-60 years), almost all those following a vegan diet and one third following a mixed diet took different food supplements.

The study results were particularly noteworthy with regard to the trace element iodine. Iodine excretion measured in urine samples provides information on how well the body is supplied with the trace element. The majority of the participants had a deficiency. The deficiency was significantly more pronounced among vegans – in one third of them, the level was below 20 micrograms per litre (μg/L), the limit defined by the World Health Organization (WHO); anything below this represents a serious shortage. A vegan diet has, however, also shown health benefits, such as a higher fibre intake and lower cholesterol levels. For both diets, about 10% of participants had an iron deficiency.

Resveratrol shows promise in reduction of stroke symptoms that can affect neuronal function

Mashhad University of Medical Sciences (Iran), November 13, 2020

According to news reporting out of Mashhad, Iran, research stated, “Stroke is one of the most important causes of death and disability in modern and developing societies. In a stroke, both the glial cells and neurons develop apoptosis due to decreased cellular access to glucose and oxygen.”

Our news reporters obtained a quote from the research from Mashhad University of Medical Sciences: “Resveratrol (3, 5, 4’-trihydroxy-trans-stilbene) as a herbal compound shows neuroprotective and glioprotective effects. This article reviews how resveratrol can alleviate symptoms after stroke to help neurons to survive by modulating some signaling pathways in glia. Various databases such as ISI Web of Knowledge, Scopus, Medline, PubMed, and Google Scholar, were searched from 2000 to February 2020 to gather the required articles using appropriate keywords. Resveratrol enhances anti-inflammatory and decreases inflammatory cytokines by affecting the signaling pathways in microglia such as AMP-activated protein kinase (5’ adenosine monophosphate-activated protein kinase, AMPK), SIRT1 (sirtuin 1) and SOCS1 (suppressor of cytokine signaling 1). Furthermore, through miR-155 overexpressing in microglia, resveratrol promotes M2 phenotype polarization. Resveratrol also increases AMPK and inhibits GSK-3b (glycogen synthase kinase 3 beta) activity in astrocytes, which release energy, makes ATP available to neurons and reduces reactive oxygen species (ROS). Besides, resveratrol increases oligodendrocyte survival, which can lead to maintaining post-stroke brain homeostasis.”

According to the news editors, the research concluded: “These results suggest that resveratrol can be considered a novel therapeutic agent for the reduction of stroke symptoms that can not only affect neuronal function but also play an important role in reducing neurotoxicity by altering glial activity and signaling.”

Vitamin D and Omega-3s bolster health in some active older people

University of Zurich, November 13, 2020

In 2030, one in three people in Europe will be over the age of 65, and all of these people will want to enjoy their old age and lead an active lifestyle. To be able to do so, however, it is crucial that people maintain their physical and mental health.

Wanted: simple and inexpensive prevention

Published last year, the VITAL study in the US indicated that vitamin D and omega-3 fatty acids did not lower the risk of developing new cancer or major cardiovascular diseases in men and women aged between 50 and 60. Now, the largest European study on old age, DO-HEALTH, has investigated the effects of these supplements on aging. The EU-funded project is led by Heike A. Bischoff-Ferrari, professor of geriatric medicine and aging research at the University of Zurich, head of clinic at the UniversityHospital Zurich and senior physician at the university clinic for geriatrics at the Waid and Triemli hospitals in Zurich.

The first findings of the three-year clinical trial published by the international team of researchers has found no effects on lower extremity function, memory or bone fracture incidence. However, the study’s findings suggest that, compared to the control group, some subgroups experienced increased benefits of vitamin D and omega-3 supplementation when it comes to lowering infection rates and systolic blood pressure.

Largest randomized double-blind study on old age

For their study, the researchers recruited 2,157 relatively healthy men and women aged 70 or older who lived at home and had no significant pre-existing conditions. About half of the participants came from Switzerland, followed by Austria, Germany, France and Portugal.

They were randomized into eight groups and received none, one, two or all three of the following interventions: supplementation of omega-3 fatty acids (1 gram/day), supplementation of vitamin D (2,000 IU/day) and/or a simple home-exercise program. Neither the trial centers nor the participants knew which group they were in. The control groups were given placebos and carried out control exercises focused on joint flexibility.

In each of the study’s three years, the seven European trial centers conducted comprehensive full-day visits to observe participants’ health and functions, while also carrying out extensive surveys over the phone every three months. The researchers examined, for example, bone and muscle density, blood pressure, memory functions, walking speed as well as important biomarkers. Moreover, they recorded events such as new diseases, infections, falls, visits to the doctor and hospital stays.

Significant positive effects for some subgroups only

“Our findings suggest that supplementation of vitamin D and omega-3s in adults aged 70 or older who lead an active lifestyle and have no pre-existing conditions does not provide any benefits when it comes to bone health, memory and muscle function. However, we believe there is an effect on infections, such as Covid-19,” says Bischoff-Ferrari.

Omega-3s reduced the risk of infections by 11% in total, in particular for upper respiratory (10%) and urinary tract infections (62%), while vitamin D lowered systolic blood pressure in men by 2.5 mmHg and the risk of infections in younger participants (70 to 74-year-old) by 16%.

“Given the high safety and low costs of these supplements as well as the high mortality associated with infections in older adults, these findings are very relevant for the health of the general population,” says Bischoff-Ferrari. The gender-specific effects of vitamin D on lowering systolic blood pressure also warrant additional research.

Placing findings in the right context

The researchers attribute the lack of effect on bone health, muscle function and memory to the relatively good health of the study’s participants, most of whom took regular exercise. Moreover, about half of the participants were so-called healthy agers, with no pre-existing conditions or vitamin D insufficiency. In addition to the supplementation prescribed by the study, they were also allowed to take 800 IUs of vitamin D daily. “The results therefore do not contradict the Federal Office of Public Health’s current recommendation on vitamin D supplementation and fall prevention for older people, nor the proven preventive effects of exercise programs,” says Bischoff-Ferrari

One-third of people with cancer use complementary and alternative medicines

University of Texas, October 31, 2020

A stunning one-third of people with a cancer diagnosis use complementary and alternative medicines such as meditation, yoga, acupuncture, herbal medicine, and supplements.

UT Southwestern Medical Center’s Dr. Nina Sanford made the discovery that’s now drawing renewed attention to habits she said cancer patients must disclose during treatment. Dr. Sanford is an Assistant Professor of Radiation Oncology who specializes in and treats cancers of the gastrointestinal tract.

Herbal supplements were the most common alternative medicine and chiropractic, or osteopathic manipulation, was the second most common, according to Dr. Sanford’s analysis of data from the Centers for Disease Control and Prevention’s National Health Interview Survey. Her findings were published in the journal JAMA Oncology.

“Younger patients are more likely to use complementary and alternative medicines and women were more likely to, but I would have thought more people would tell their doctors,” Dr. Sanford said, referring to the finding that 29 percent of people who use complementary and alternative medicine did not tell their physicians. Many survey respondents said they did not say anything because their doctors did not ask, or they did not think their doctors needed to know.

Dr. Sanford and other cancer specialists agree this is concerning, especially in the case of herbal supplements.

“You don’t know what’s in them,” Dr. Sanford said. “Some of these supplements are kind of a mishmash of different things. Unless we know what’s in them, I would recommend patients avoid using them during radiation because there’s likely not data on certain supplements, which could interfere with treatment. With radiation specifically, there is concern that very high levels of antioxidants could make radiation less effective.”

Dr. David Gerber, a lung cancer specialist and a Professor of Internal Medicine and Population and Data Sciences at UTSW, said physicians need to know if their patients use herbal supplements because they can completely throw off traditional cancer treatments.

“They may interact with the medicines we’re giving them, and through that interaction it could alter the level of the medicine in the patient,” he said. “If the levels get too high, then toxicities increase, and if the levels get too low, the efficacy would drop.”

Nancy Myers wanted to use supplements during her 2015-2017 cancer treatments, but she ran it by her doctors first.

“I would ask the physician, ‘Could I?’ and everyone said, ‘No, we don’t know how that interacts with your conventional medicine,’ so I respected that,” the 47-year-old mother of four said. Only after treatment did she start taking turmeric, omega-3, vitamin D, and vitamin B6.

“I have plenty of friends in this cancer journey who I’ve met who take supplements. A lady I met recently takes 75 supplements a day. It takes her two hours to package her supplements every week,” she said.

Ms. Myers said every person in her cancer support group uses some kind of alternative medicine. In addition to supplements, she practices meditation and yoga with guidance from a smartphone app.

“It’s what we can control. We can’t control the whole cancer,” she said. “It helps because it takes your mind off just thinking about it.”

She said she knows of some people with cancer who use only alternative medicine – and no traditional medical treatments. Dr. Sanford said this is a dangerous approach that could be fatal. The most famous case of this was Apple founder Steve Jobs, who reportedly used special diets, acupuncture, and other alternatives after receiving a diagnosis of pancreatic cancer. He turned to traditional medicine late in his battle with cancer and died in 2011.

While doctors are highly cautious about the use of herbs and other supplements during treatment, they are much more open to meditation and yoga as practices that can help patients cope with the shock of a cancer diagnosis and the stress of chemotherapy, radiation, and surgery.

“We strongly advise patients to stay active and engage in exercise during treatment,” Dr. Sanford said. “A common side effect of radiation is fatigue. I let the patients know that the patients who feel the most fatigue are the ones who are the most sedentary and that those who are doing exercise are the ones who frequently have the most energy.”

Belindy Sarembock, 53, of Dallas, said she practiced yoga during her treatments for breast cancer. She started the classes with skepticism and quickly became convinced of the benefits.

“I was one who would have laughed at yoga before breast cancer, but now it just helps me so much,” she said. “It’s just so relaxing, I just feel so good after I leave. It’s just so peaceful. For your body, I can’t think of anything better than that.”

She said she had neuropathy or nerve damage from chemotherapy, and yoga almost immediately took the pain away.

“I couldn’t get onto my toes. After the second time of going to yoga, I was able to go onto my toes,” she said. “I wish I would have known about the yoga earlier. It was just such a benefit and helped me so much. I highly recommend it to anyone.”

Be mindful: Study shows mindfulness might not work as you expect

University of Buffalo, November 15, 2020

If dispositional mindfulness can teach us anything about how we react to stress, it might be an unexpected lesson on its ineffectiveness at managing stress as it’s happening, according to new research from the University at Buffalo.

When the goal is “not to sweat the small stuff,” mindfulness appears to offer little toward achieving that end.

The findings, published in the journal Personality and Social Psychology Bulletin, which measured the cardiovascular responses of 1,001 participants during stressful performance tasks, run contrary to previous research and pop culture assertions of how being mindful offers stress relief and coping benefits.

Where earlier work in this area suggests how mindfulness may help people manage active stressors, the current paper finds evidence for an opposite response. In the midst of stress, mindful participants demonstrated cardiovascular responses consistent with greater care and engagement. Put another way, they actually were “sweating the small stuff.”

Even more curiously, although the study’s participants demonstrated no physiological signs associated with positive stress responses, they did report having a positive experience afterward.

“What’s surprising, and particularly striking about our results, is that mindfulness didn’t seem to affect whether people had a more positive stress response in the moment,” said Thomas Saltsman, a researcher in UB’s psychology department and the paper’s lead author. “Did more mindful people actually feel confident, comfortable and capable while engaged in a stressful task? We didn’t see evidence of that, despite them reporting feeling better about the task afterward.”

Mindfulness does have benefits, but appears to be limited in what it can accomplish while people are actively engaged in stressful tasks, like taking a test, giving a speech or sitting for a job interview. Instead, being mindful may only benefit people’s perception of their stress experience after it has ended.

“Although our findings seem to go against a wholesome holy grail of stress and coping benefits associated with dispositional mindfulness, we believe that they instead point to its possible limitations,” says Saltsman. “Like an alleged holy grail of anything, its fruits are likely finite.”

Saltsman describes dispositional mindfulness as having a focused attention on the present. It’s a mindset that tries to avoid ruminating on past realities or considering future possibilities or consequences. It’s about being non-judgmental and relaxing critical interpretations. Mindfulness can be approached with formal training, but people can also be dispositionally higher or lower in mindfulness, which was the focus of their study.

Those high in dispositional mindfulness report greater well-being. They tend not to dwell on past events, and claim to manage stress well.

“Although those benefits seem unambiguous, the specific ways in which mindfulness should impact people’s psychological experiences during stress remain unclear,” says Saltsman. “So we used cardiovascular responses to capture what people were experiencing in a moment of stress, when they’re more or less dispositionally mindful.”

By measuring cardiovascular responses, Saltsman and the other researchers, including Mark Seery, an associate professor of psychology at UB, can tap into participants’ experiences during moments of stress—in this case, giving a speech or taking a reasoning-ability test.

Those responses include heart rate and how hard the heart is pumping. When people care more about the task they are completing, Seery says, their heart rate increases and beats harder. Other measures, like how much blood the heart is pumping and the degree to which blood vessels dilate, indicate how confident or capable one feels during the task.

“One thing these results say to me, in terms of what the average person is expecting when they casually get into mindfulness, is that what it’s actually doing for them could very well be mismatched from their expectations going in,” says Seery. “And this is an impressively large sample of more than a thousand participants, which makes the results particularly convincing.”

One-year effects of omega-3 treatment on fatty acids, oxylipins and related bioactive lipids

Brigham and Women’s Hospital, November 11, 2020

According to news reporting out of the Brigham and Women’s Hospital , research stated, “Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear.”

Our news correspondents obtained a quote from the research from Brigham and Women’s Hospital: “We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined these VITAL200, a nested substudy of 200 subjects balanced on demographics and treatment and randomly selected from the Vitamin D and Omega-3 Trial (VITAL). VITAL is a randomized double-blind trial of 840 mg/d eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) vs. placebo among 25,871 individuals. Small polar bioactive lipid features, oxylipins and FAs from plasma and red blood cells were measured using three independent assaying techniques at baseline and one year. The Women’s Health Study (WHS) was used for replication with dietary n-3 intake. Randomized n-3 treatment led to changes in 143 FAs, oxylipins and bioactive lipids (False Discovery Rate (FDR) < 0.05 in VITAL200, validated (* * p* * -values < 0.05)) in WHS with increases in 95 including EPA, DHA, n-3 docosapentaenoic acid (DPA-n3), and decreases in 48 including DPA-n6, dihomo gamma linolenic (DGLA), adrenic and arachidonic acids.”

According to the news reporters, the research concluded: “N-3 related changes in the bioactive lipidome were heterogeneously associated with changes in clinical lipid and inflammatory biomarkers. N-3 treatment significantly modulates the bioactive lipidome, which may contribute to its clinical benefits.”

Vitamin C’s effectiveness against COVID may hinge on vitamin’s natural transporter levels

Medical College of Georgia Center for Healthy Aging, November 12, 2020

High doses of vitamin C under study for treating COVID-19 may benefit some populations, but investigators exploring its potential in aging say key factors in effectiveness include levels of the natural transporter needed to get the vitamin inside cells.

Age, race, gender, as well as expression levels and genetic variations of those vitamin C transporters that make them less efficient, all may be factors in the effectiveness of vitamin C therapy against COVID-19 and other maladies, investigators at the Medical College of Georgia Center for Healthy Aging report in a commentary in the journal Aging and Disease.

The investigators recommend that those factors be considered in the design and execution of clinical trials, and when trial results are analyzed, for COVID-19 as well as other conditions, says Dr. Sadanand Fulzele, aging researcher and the article’s corresponding author.

The novel nature and lack of immunity against the coronavirus has prompted a worldwide pursuit of effective treatments for COVID-19, they write. That includes repurposing drugs with known safety profiles, including Vitamin C, an established immune system booster and antioxidant, which made it a logical choice to explore in COVID-19. Both strategies are needed in response to infection with the novel coronavirus to ensure a strong immune response to stop the virus from replicating in the body, and to avoid the over-the-top, destructive immune response the virus itself can generate if it does.

There are at least 30 clinical trials underway in which vitamin C, alone or in combination with other treatments, is being evaluated against COVID-19, some with doses up to 10 times the recommended 65 to 90 milligrams daily of vitamin C.

Factors like whether or not vitamin C can get inside the cell, likely are an issue in the effectiveness the therapies ultimately show, says Dr. Carlos M. Isales, co-director of the MCG Center for Healthy Aging and chief of the MCG Division of Endocrinology, Diabetes and Metabolism.

In fact, without adequate transporters on a cell’s surface to get the water-soluble vitamin past the lipid layer of cell membranes, particularly large doses may enable the vitamin to cluster around the outside of cells where it actually starts producing oxidants, like damaging reactive oxygen species, rather than helping eliminate them, says Isales, a study coauthor.

“We think it’s important to look at transporter expression,” Fulzele says.

They suspect low transporter expression is a factor in the mixed results from vitamin C’s use in a variety of other conditions. Clinical trials in osteoarthritis, for example, an autoimmune disease where a misdirected immune system is attacking the joints, has gotten mixed results, Fulzele says. However its usage in other viral-induced problems, like potentially deadly sepsis, has shown benefit in reducing organ failure and improving lung function in acute respiratory distress syndrome, which is also a major cause of sickness and death with COVID-19.

At the time their Aging and Disease paper was published, there were not yet published studies of the efficacies of high-dose, intravenous vitamin studies underway for COVID-19.

Fulzele, who works on vitamin C in aging, and others have shown that some conditions, like osteoarthritis and even normal aging, are associated with significant downregulation of at least one subtype of vitamin C transporter.

In fact, part of the paradox and concern with COVID-19 is that those most at risk mostly have both lower levels of vitamin C before they get sick and fewer transporters to enable the vitamin to be of benefit if they get more, Fulzele says.

Many of those most at risk from COVID-19, including individuals who are older, Black, male and with chronic medical conditions like osteoarthritis, hypertension and diabetes, tend to have lower levels of vitamin C, another reason vitamin C therapy would be considered a reasonable treatment, Isales says. The investigators also note that patients may develop a vitamin C deficiency over the course of their COVID-19 illness since, during an active infection, vitamin C is consumed at a more rapid rate. Insufficient levels can augment the damage done by an overzealous immune response.

While not routinely done, transporter expression can be measured today using PCR technology, a method also used for novel coronavirus as well as influenza testing. While increasing transporter expression is not yet doable in humans, one of Fulzele’s many research goals is to find a drug or other method to directly increase expression, which should improve the health of older individuals as well as those with other medical conditions that compromise those levels.

He notes that reduced transporter levels that occur naturally with age are a factor in the reduced immune function that also typically accompanies aging. That means that even when a 60-year-old and 20-year-old both have a healthy diet in which they consume similar, sufficient amounts of vitamin C, the vitamin is not as effective at boosting the older individual’s immune response. Reduced immune function in older individuals is known to put them at increased risk for problems like cancer and COVID-19.

Low vitamin C levels also have been correlated with higher mortality in older individuals from causes like cardiovascular disease. High oxidative stress, a major factor in conditions like cardiovascular disease as well as aging and now COVID-19, also is associated with significantly reduced expression of the vitamin C transporter.

Isales and Fulzele doubt that taking a lot of vitamin C is a good preventive strategy against COVID-19, except in those individuals with a known deficiency.

Vitamin C is an essential vitamin, which means people have to consume it in their food or supplements. Foods naturally high in vitamin C include oranges, potatoes, tomatoes, broccoli and Brussels sprouts. The vitamin’s diverse roles in the body also include formation of blood vessels, collagen and cartilage.

Emerging role of vitamin C in prevention and treatment of novel respiratory virus

University of Otago (New Zealand), November 11, 2020

According to news reporting out of Christchurch, New Zealand, research stated, “Investigation into the role of vitamin C in the prevention and treatment of pneumonia and sepsis has been underway for many decades. This research has laid a strong foundation for translation of these findings into patients with severe coronavirus disease (COVID-19).”

Our news correspondents obtained a quote from the research from University of Otago: “Research has indicated that patients with pneumonia and sepsis have low vitamin C status and elevated oxidative stress. Administration of vitamin C to patients with pneumonia can decrease the severity and duration of the disease. Critically ill patients with sepsis require intravenous administration of gram amounts of the vitamin to normalize plasma levels, an intervention that some studies suggest reduces mortality. The vitamin has pleiotropic physiological functions, many of which are relevant to COVID-19. These include its antioxidant, anti-inflammatory, antithrombotic and immuno-modulatory functions. Preliminary observational studies indicate low vitamin C status in critically ill patients with COVID-19. There are currently a number of randomized controlled trials (RCTs) registered globally that are assessing intravenous vitamin C monotherapy in patients with COVID-19. Since hypovitaminosis C and deficiency are common in low-middle-income settings, and many of the risk factors for vitamin C deficiency overlap with COVID-19 risk factors, it is possible that trials carried out in populations with chronic hypovitaminosis C may show greater efficacy. This is particularly relevant for the global research effort since COVID-19 is disproportionately affecting low-middle-income countries and low-income groups globally. One small trial from China has finished early and the findings are currently under peer review. There was significantly decreased mortality in the more severely ill patients who received vitamin C intervention. The upcoming findings from the larger RCTs currently underway will provide more definitive evidence.”

According to the news reporters, the research concluded: “Optimization of the intervention protocols in future trials, e.g., earlier and sustained administration, is warranted to potentially improve its efficacy. Due to the excellent safety profile, low cost, and potential for rapid upscaling of production, administration of vitamin C to patients with hypovitaminosis C and severe respiratory infections, e.g., COVID-19, appears warranted.”

Beneficial effects of intermittent fasting: an update on mechanism, and the role of circadian rhythm and gut microbiota

Sun Yat-sen University (China), November 11, 2020

According to news originating from Guangzhou, People’s Republic of China, research stated, “Importance: There is accumulating evidence that intermittent fasting (IF) is connected to improved health condition and longevity time-restricted feeding (TRF) is the most recognized and extensively studied model of IF. To investigate the underlying mechanism of pleiotropic benefits of IF and hint the most advantageous feeding pattern for humans.”

Our news journalists obtained a quote from the research from Sun Yat-sen University, “Evidence review: We searched MEDLINE, EMBASE, Cochrane Library and Google Scholar by 2020 April for publications on IF or TRF and their mechanisms. Studies include animal models and human cohorts. One important mechanism is that IF allows certain period of fasting time, in which our bodies activate pathways of repair and rejuvenation. Moreover, the advantages of IF, especially TRF over total caloric restriction (CR) provided bases for various animal and human studies which suggested that the feeding-fasting rhythm stimulates the fluctuation of our gut microbiota and a series of subsequent molecular alterations, which in turn restored a healthier circadian clock that resembled our inherent clock formed throughout millions of years of homo sapiens history.”

According to the news editors, the research concluded: “Conclusions and Relevance for Reviews: Complete understanding of the mechanism leading to the beneficial effects of IF paves the way for tailored dietary regimen to combat a wide range of diseases and ill health conditions.”

This research has been peer-reviewed.

Valerian Quality, Storage Issues May Affect Sleep Outcomes

Chiba and Nagasaki universities (Japan), November 1, 2020

Valerian (Valeriana officinalis L.) may be a safe and effective herbal sleep aid; however quality control issues may affect outcomes, according to the findings of a recently published systematic review and meta-analysis.

While valerian is considered a popular herbal supplement for managing sleep disorders, study outcomes related to its effectiveness have been inconsistent. This review, which included a total of 60 studies (n=6894), aimed to determine the reason for this inconsistency as well as to provide an overview of the role of valerian for other disorders associated with sleep problems.

Meta-analyses were performed to assess the efficacy of valerian on improving subjective sleep quality (10 studies, n=1065), as well as to evaluate its role in reducing anxiety (8 studies, n=535). “Repeated treatments with the whole root/rhizome consistently promoted sleep quality at 450-1410mg per day for 4-8 weeks, whereas valerian extracts 300-600mg per day for 5 days-4 weeks resulted in inconsistent outcomes,” the study authors reported.

In their review, the authors found that the variability in the quality of valerian extracts was dependent on the extraction solvents utilized during the study. Additionally, findings revealed limited information on storage conditions, such as temperature and storage duration, used during each study. “The absence of such information limits the discussion as to why some extracts were ineffective while others exhibited effectiveness in those clinical trials,” the authors noted.

As for safety, findings revealed no severe adverse events with valerian intake in patients 7 to 80 years old. Valerian was also not observed to have a significant impact on cytochrome (CYP) P1A2, 2D6, 2E1, or 3A4/5.

Based on their findings, the authors concluded that revisions to quality control processes for valerian were needed; however, for the time being, “the usage of whole herbal substances (root/rhizome), rather than extracts, may be the way to obtain optimal efficacy.”

Oh my aching back: Do yoga, tai chi or qigong help?

Florida Atlantic University, November 6, 2020

It’s a pain. About 80 percent of adults in the United States will experience lower back pain at some point. Treating back pain typically involves medication, including opioids, surgery, therapy and self-care options. Efforts to reduce opioid use and increase physically based therapies to reduce pain and increase physical function and safety are crucial.

Patients are often advised to use non-pharmacological treatments to manage lower back pain such as exercise and mind-body interventions. But, do they really help? In a review published in the journal Holistic Nursing Practice, researchers from Florida Atlantic University’s College for Design and Social Inquiry and Christine E. Lynn College of Nursing evaluated the evidence of effects of three movement-based mind-body interventions on chronic low back pain. They examined yoga, tai chi, which combines gentle physical exercise and stretching with mindfulness, and qigong, a traditional Chinese meditative movement therapy focused on body awareness and attention during slow, relaxed, and fluid repetitive body movements. Little is known about the effects of movement-based mind-body intervention, in particular qigong and tai chi.

Researchers compared and contrasted yoga, tai chi and qigong by examining frequency and duration of these interventions; primary and secondary outcomes; attrition rates and possible adverse events; and results. Findings from their review provide empirical evidence regarding the benefits of yoga, tai chi, and qigong, which have been recommended by health care providers for patients with lower back pain.

“Back pain is a major public health issue often contributing to emotional distress such as depression and anxiety, as well as sleep issues and even social isolation,” said Juyoung Park, Ph.D., corresponding author and an associate professor in the Phyllis and Harvey Sandler School of Social Work within FAU’s College for Design and Social Inquiry. “We reviewed data to determine the effects of movement-based mind-body interventions on chronic back pain, psychological factors, coping strategies, and quality of life in people suffering with back pain. Our goal was to provide a comprehensive assessment of the effects of these interventions to be able to offer information across disciplines to implement evidence-based interventions to reduce such pain.”

Of the 625 peer-reviewed articles the researchers identified, 32 met inclusion criteria and were included in the review. Results found that the majority of these articles showed movement-based mind-body interventions to be effective for treatment of low back pain, reporting positive outcomes such as reduction in pain or psychological distress such as depression and anxiety, reduction in pain-related disability, and improved functional ability. Among the key findings, researchers discovered that longer duration and high-dose yoga intervention showed reductions in back pain while tai chi reduced acute lower back pain in males in their 20s. Tai chi also was more effective than stretching for lower back pain in young males. In the general community, tai chi showed greater reductions in pain intensity, bothersomeness of pain symptoms, and pain-related disability than the control intervention. Because there are only three qigong studies to date, it was unclear to the researchers whether this intervention is useful in treating chronic lower back pain. Existing research suggests positive benefits of yoga, however, tai chi and qigong for lower back pain are still under-investigated.

“Two of the studies we examined in our review were focused on the effects of movement modality, specifically yoga, in veterans. Many military veterans and active duty military personnel experience chronic low back pain and are affected by this pain more than the general population,” said Cheryl Krause-Parello, Ph.D., co-author, a professor and director of Canines Providing Assistance to Wounded Warriors (C-P.A.W.W.) within FAU’s Christine E. Lynn College of Nursing, and a faculty fellow of FAU’s Institute for Human Health and Disease Intervention (I-HEALTH). “Our review provides emerging evidence that movement-based mind-body interventions could benefit veterans and others experiencing chronic low back pain.”

The review included both randomized and nonrandomized studies with a total of 3,484 subjects ages 33 to 73 years old. Study sample sizes ranged from 25 to 320 subjects. The majority of articles reported on yoga (25), followed by tai chi (four), and qigong (three). Most of the yoga studies were conducted in India, followed by the U.S., while other studies were conducted in Australia (tai chi) and Germany (qigong).

People with chronic low back pain are at increased risk of functional limitations, job-related disability, and potential long-term disability. Moreover, the economic burden of chronic low back pain is high due to the cost of medications such as opioids, procedures, hospitalization, surgical treatment, and absence from work.

“Yoga, tai chi and qigong could be used as effective treatment alternatives to pain medications, surgery, or injection-based treatments such as nerve blocks, which are associated with high incidence of adverse effects in treating lower back pain,” said Park. “We need more clinical trials and empirical evidence so that clinicians can prescribe these types of interventions with more confidence for managing lower back pain in their patients.”