Tuesday Apr 27, 2021
The Gary Null Show - 04.27.21
Anti-aging compound improves muscle glucose metabolism in people
Washington University School of Medicine in St. Louis, April 25, 2021
A natural compound previously demonstrated to counteract aspects of aging and improve metabolic health in mice has clinically relevant effects in people, according to new research at Washington University School of Medicine in St. Louis.
A small clinical trial of postmenopausal women with prediabetes shows that the compound NMN (nicotinamide mononucleotide) improved the ability of insulin to increase glucose uptake in skeletal muscle, which often is abnormal in people with obesity, prediabetes or Type 2 diabetes. NMN also improved expression of genes that are involved in muscle structure and remodeling. However, the treatment did not lower blood glucose or blood pressure, improve blood lipid profile, increase insulin sensitivity in the liver, reduce fat in the liver or decrease circulating markers of inflammation as seen in mice.
The study, published online April 22 in the journal Science, is the first randomized clinical trial to look at the metabolic effects of NMN administration in people.
Among the women in the study, 13 received 250 mg of NMN orally every day for 10 weeks, and 12 were given an inactive placebo every day over the same period.
"Although our study shows a beneficial effect of NMN in skeletal muscle, it is premature to make any clinical recommendations based on the results from our study," said senior investigator Samuel Klein, MD, the William H. Danforth Professor of Medicine and Nutritional Science and director of the Center for Human Nutrition. "Normally, when a treatment improves insulin sensitivity in skeletal muscle, as is observed with weight loss or some diabetes medications, there also are related improvements in other markers of metabolic health, which we did not detect in our study participants."
The remarkable beneficial effects of NMN in rodents have led several companies in Japan, China and in the U.S. to market the compound as a dietary supplement or a neutraceutical. The U.S. Food and Drug Administration is not authorized to review dietary supplement products for safety and effectiveness before they are marketed, and many people in the U.S. and around the world now take NMN despite the lack of evidence to show clinical benefits in people.
The researchers studied 25 postmenopausal women who had prediabetes, meaning they had higher than normal blood sugar levels, but the levels were not high enough to be diagnosed as having diabetes. Women were enrolled in this trial because mouse studies showed NMN had the greatest effects in female mice.
NMN is involved in producing an important compound in all cells, called nicotinamide adenine dinucleotide (NAD). NAD plays a vital role in keeping animals healthy. Levels of NAD decline with age in a broad range of animals, including humans, and the compound has been shown to contribute to a variety of aging-associated problems, including insulin resistance in studies conducted in mice. Supplementing animals with NMN slows and ameliorates age-related decline in the function of many tissues in the body.
Co-investigator Shin-ichiro Imai, MD, Ph.D., a professor of developmental biology and of medicine who has been studying NMN for almost two decades and first reported on its benefits in mice said, "This is one step toward the development of an anti-aging intervention, though more research is needed to fully understand the cellular mechanisms responsible for the effects observed in skeletal muscle in people."
Insulin enhances glucose uptake and storage in muscle, so people who are resistant to insulin are at increased risk for developing Type 2 diabetes. But the researchers caution that more studies are needed to determine whether NMN has beneficial effects in the prevention or management of prediabetes or diabetes in people. Klein and Imai are continuing to evaluate NMN in another trial involving men as well as women.
High dose of vitamin D fails to improve condition of moderate to severe COVID-19 patients
University of São Paulo's Medical School (Brazil), April 26, 2021
Can a high dose of vitamin D administered on admission to hospital improve the condition of patients with moderate or severe COVID-19? The answer is no, according to a Brazilian study published in the Journal of the American Medical Association (JAMA).
The article reports a randomized, double-blind, placebo-controlled clinical trial, the kind of study considered the gold standard to evaluate drug efficacy. It was conducted with FAPESP's support by researchers at the University of São Paulo's Medical School (FM-USP), who recruited 240 patients treated at Hospital das Clínicas (HC), the hospitalcomplex run by FM-USP, and the Ibirapuera field hospital in São Paulo City in June-August 2020.
"In vitro studies or trials with animals had previously shown that in certain situations vitamin D and its metabolites can have anti-inflammatory and anti-microbial effects, as well as modulating the immune response. We decided to investigate whether a high dose of the substance could have a protective effect in the context of an acute viral infection, reducing either the inflammation or the viral load," Rosa Pereira, principal investigator for the project, told Agência FAPESP.
The volunteers were randomly divided into two groups, one of which was given vitamin D3 in a single dose of 200,000 units (IU) dissolved in a peanut oil solution. The other group was given only the peanut oil solution. All participants were treated according to the standard protocol for hospital treatment of the disease, which includes administration of antibiotics and anti-inflammatory drugs.
The main purpose was to see if acute supplementation would affect the length of hospital stay for these patients, but the researchers also wanted to find out whether it would mitigate the risks of admission to the intensive care unit (ICU), intubation and death.
No significant difference between the groups was observed for any of these clinical outcomes. According to Pereira, the study was designed above all to assess the impact on hospital stay and a larger number of volunteers would be needed to achieve a scientifically acceptable estimate of the effect on mortality.
"So far we can say there's no indication to administer vitamin D to patients who come to the hospital with severe COVID-19," she said.
For Bruno Gualano, a researcher at FM-USP and penultimate author of the article, the findings show that at least for now there is no "silver bullet" for the treatment of COVID-19. "But that doesn't mean continuous use of vitamin D can't have beneficial effects of some kind," he said.
Ideal dose
Pereira is currently leading a study at FM-USP to find out whether subjects with sufficient circulating levels of vitamin D combat infection by SARS-CoV-2 better than those with insufficient levels of the nutrient.
The ideal level of vitamin D in the blood and the daily supplementation dose vary according to age and overall health, she explained. Older people and patients with chronic diseases including osteoporosis should have more than 30 nanograms per milliliter of blood (ng/mL). For healthy adults, 20 ng/mL is an acceptable threshold.
"The ideal approach is case-by-case analysis, if necessary dosing the substance periodically by means of blood work, with supplementation if a deficiency is detected," Pereira said.
Sufficient serum vitamin D before 20 weeks of pregnancy reduced risk of gestational diabetes mellitus
Fudan University Obstetrics and Gynecology Hospital (China), April 16, 2021
A new study on Nutritional and Metabolic Diseases and Conditions - Obesity and Diabetes is now available. According to news originating from Shanghai, People’s Republic of China, by NewsRx correspondents, research stated, “Our aim was to evaluate the relationship between serum vitamin D levels before 20 weeks of pregnancy and the risk of gestational diabetes mellitus. This study is a retrospective study.”
Our news journalists obtained a quote from the research from Fudan University Obstetrics and Gynecology Hospital, “We analyzed the relationship between serum 25 (OH) D level before 20 weeks of pregnancy (first antenatal examination) and the risk of gestational diabetes mellitus. Age, parity and pre-pregnancy body mass index were used as confounding factors. 8468 pregnant women were enrolled in this study between January 2018 and March 2020 at the Obstetrics and Gynecology Hospital of Fudan University. Adjusted smoothing splinespline plots, subgroup analysis and multivariate logistic regression analysis was conducted to estimate the relative risk between 25(OH)D and gestational diabetes mellitus. After fully adjusting the confounding factors, serum vitamin D is a protective factor in gestational diabetes mellitus (OR=0.90). Compared with vitamin D deficiency, vitamin D insufficiency (OR=0.78), sufficience (OR=0.82) are a protective factor for gestational diabetes mellitus. Sufficience vitamin D before 20 weeks of pregnancy is a protective factor for gestational diabetes mellitus. Vitamin D>20 ng/mL can reduce the risk of GDM, which is not much different from the effect of >30 ng/mL.”
According to the news editors, the research concluded: “The protective effect of vitamin D is more significant in obese pregnant women.”
Review summarizes known links between endocrine disruptors and breast cancer risk
University of Eastern Finland, April 20, 2021
Exposure to certain endocrine-disrupting chemicals could elevate the risk of breast cancer, according to a new comprehensive systematic review of epidemiological research. However, for many chemicals, evidence is inconsistent or still limited. The review was carried out by researchers at the universities of Hong Kong and Eastern Finland and published in Critical Reviews in Food Science and Nutrition.
Endocrine-disrupting chemicals (EDCs) can interfere with the body's hormonal system, also called the endocrine system, and are widely present in the environment. They originate from a variety of sources, including pesticides, plasticisers and other industrial and pharmaceutical chemicals, as well as natural sources. Humans are often exposed to EDCs through food, but other possible exposure routes include drinking water, skin contact and air.
Breast cancer accounts for the majority of women's cancers. There has been an increasing interest in the role of estrogene-mimicking EDCs, so called xenoestrogens, in the development of breast cancer. They comprise a broad range of pesticides, synthetic chemicals, phytoestrogens and certain mycotoxins. The researchers reviewed 131 epidemiological studies evaluating the link between xenoestrogen exposure and breast cancer. Most studies assessed exposures by measuring the EDCs and their metabolites in urine, serum, plasma or adipose tissues.
Some may be genetically more vulnerable to EDCs
According to the review, the nowadays widely banned pesticide DDT is one of the most studied EDCs in relation to breast cancer risk. Out of 43 epidemiological studies, eleven reported positive associations between DDT or its metabolites in lipid, serum or plasma and breast cancer incidence. Nine reported higher DDT levels among women with breast cancer than among controls. In a few studies, DDT was linked to estrogen-positive breast cancer or the association to breast cancer risk depended on genotype.
Polychlorinated biphenyls, PCBs, are a large group of compounds earlier much used in electrical devices, surface coatings and other purposes. The review of 50 studies found the association between total PCBs and breast cancer risk to be inconsistent. However, 19 studies linked certain PCBs to a higher breast cancer incidence. Similar to DTT, PCBs accumulate in the adipose tissue and in the food chain and can be excreted in breast milk.
Perfluorooctanoid acid (PFOA) found in some food packaging and cookware was linked to breast cancer risk in three out of five epidemiological studies. Some studies found an association between cancer risk and certain genotypes both for PCBs and PFOAs.
DDT, PCBs ja PFOA are POP substances, persistent organic pollutants, the use of which is strictly regulated. DDT ja PCBs are old POP substances and their levels in the environment are decreasing. PFOA is a newer POP substance.
Phytoestrogens were found beneficial in some, but not all studies
Phytoestrogens are natural plant estrogens that have been suggested to prevent breast cancer. Genistein is a phytoestrogen found in soy products. The review included 29 epidemiological studies focusing on genistein, 18 of which linked it to a lower breast cancer risk, although some only in certain age groups or populations.
For most EDCs included in the review, the link to breast cancer has been investigated in only a few epidemiological studies. Phtalates and bisphenol A (BPA), for example, are used in plastic packaging and can transfer to food. According to the review, four out of six studies linked phthalates to increased breast cancer risk. BPA was linked to more aggressive tumours in one study, but two other epidemiological studies found no link to breast cancer.
Parabens are common preservatives in foods and cosmetic products and considered possible endocrine disruptors. The only epidemiological study on the topic reported a link between paraben exposures, breast cancer risk and mortality following breast cancer.
Oral contraceptive use was linked to an increased breast cancer risk in seven out of eight epidemiological studies, but there were controversies on how duration or discontinuation of oral contraceptive use affected the risk.
The review also included the herbicide atrazine, the industrial by-product dioxine, mycotoxins produced by food and crop molds, and PBDEs found in household furniture coatings and appliances, but epidemiological studies on their links to breast cancer risk were still scarce and often inconsistent.
The writers point out that for EDCs to disrupt endocrine functions, dose, time, duration and age at exposure all matter. In addition, as multiple EDCs coexist in the environment, more research is needed to evaluate their interactive effects on breast cancer risk.
The review also suggests that genotypes could determine whether EDC exposure affects breast cancer risk, and more research is needed on this topic. "One example is the polymorphism of the CYP1A1 gene, which is responsible for estrogen metabolism."
According to the writers, next-generation technologies, such as genome sequencing, proteomics or epigenomics, can help identify new exposure biomarkers with better sensitivity and specificity. "These technologies will also pave way to better assessment of past exposure and prediction of future risks, by taking into account an individual's genetic profile."
Grape seed extract may protect gut from inflammation: Study
Universitat Rovira i Virgili (Spain), April 25, 2021
Proanthocyanidin-rich grape seed extracts may protect the intestines from the deleterious effects of a high-fat/high-carbohydrate diet, according to data from a rat study.
A high-fat/high-carbohydrate diet or Western diet has been reported to produce changes in the intestine, explained researchers from the Universitat Rovira i Virgili in Tarragona, Spain.
“Concretely, several recent studies have provided compelling new evidence to suggest that changes in the epithelial barrier function and intestinal inflammation are associated with and could even lead to altered regulation of body weight and glucose homeostasis,” they added.
“The main consequence of the gut barrier dysfunction has been proposed to be the entry of toxins from the intestinal lumen, which can trigger local inflammation or gain access to the circulation and induce systemic inflammation through cytokine release.”
Their new research indicated that a grape seed proanthocyanidin extract (GSPE) may protect the gut from such harmful effects.
Study details
Data published in Molecular Nutrition and Food Research reveals that supplementing the diet of lab rats with medium or high-dose proanthocyanidins had beneficial impacts on intestinal inflammation, oxidative stress, and barrier function. The medium dose was 25 mg/kg, which is a dose similar to the dietary proanthocyanidin intake in humans, explained the researchers. The high dose (50 mg/kg) would exceed the dietary proanthocyanidin intake in humans.
Thirty-six week-old rats were fed a Western diet for 15 weeks and then divided into one of four supplementation groups, receiving 0 mg/kg (control), 5 mg/kg (low dose), 25 mg/kg, or 50 mg/kg for an additional three weeks.
Results showed that intestinal inflammation, assessed by measuring myeloperoxidase (MPO) activity, significantly increased in the control animals, but these increases were reduced in the rats receiving the grape seed extract.
In addition, significant reductions in plasma levels of reactive oxygen species were observed in the medium and high dose groups, compared to the control group.
Tight junctions
The researchers also examined the function of the intestinal barrier, and looked specifically at so-called tight junctions (TJ) between cells in the lining of the intestine – the epithelium. On one side is the intestinal cavity and on the other is a mass of cells and tissues. In a healthy system, materials in the cavity find their way into tissues by passing through the cells, which controls which substances pass through. In an unhealthy system, the tight junctions are not so tight and materials can bypass the cells and find their way into tissues via the tight junctions. This increase in intestinal permeability has been referred to as "leaky gut".
“Another point of interest in this study was to evaluate whether GSPE could modulate the alterations in the permeability of the intestinal barrier that are related to the state of intestinal inflammation,” wrote the researchers. “Our findings indicate that the TJ proteins were negatively associated with measures of adiposity and with the circulating levels of [triglycerides]. These are not causal associations, but they suggest that increased adiposity is accompanied by lower expression of TJ components, which is in agreement with the hypothesis that obesity and a [high-fat diet] are associated with increased intestinal permeability. Then, given the importance of having a healthy barrier function, dietary interventions that can modulate the intestinal permeability might afford an effective tool for the prevention and treatment of metabolic diseases associated with obesity.”
The researchers concluded: “Our findings indicate that orally administered GSPE modulates the intestinal inflammation, oxidative stress, and possibly the barrier function. Based on these findings, our data suggest that nutritional and/or therapeutic interventions focused on gut health and modulation of the intestinal permeability should be extensively explored in the context of obesity.”
Antidepressant use in pregnancy tied to affective disorders in offspring; no causal link
Mount Sinai Hospital, April 12, 2021
Major depressive disorder is highly prevalent, with one in five people experiencing an episode at some point in their life, and is almost twice as common in women than in men. Antidepressants are usually given as a first-line treatment, including during pregnancy, either to prevent the recurrence of depression, or as acute treatment in newly depressed patients. Antidepressant use during pregnancy is widespread and since antidepressants cross the placenta and the blood-brain barrier, concern exists about potential long-term effects of intrauterine antidepressant exposure in the unborn child.
Using the Danish National Registers to follow more than 42,000 singleton babies born during 1998-2011 for up to 18 years, researchers at the Icahn School of Medicine at Mount Sinai investigated whether exposure to antidepressants in the womb would increase the risk of developing affective disorder like depression and anxiety in the child. In a study published April 5 in Neuropsychopharmacology,the scientists found that children whose mothers continued antidepressants during pregnancy had a higher risk of affective disorders than children whose mothers stopped taking antidepressants before pregnancy. However, to understand whether the underlying disorder for which the antidepressant was given or the medication itself was linked to the child's risk of developing an affective disorder, they also studied the effect of paternal antidepressant use during pregnancy and similarly, found that children of fathers who took antidepressants throughout pregnancy had a higher risk for affective disorders. Thus, the research team speculates that rather than being an intrauterine effect, the observed link is most likely due to the parental mental illness underlying the antidepressant use.
"Approximately half of women who use antidepressants before pregnancy decide to discontinue use either before or during pregnancy due to concerns about the negative consequences for their child," said Anna-Sophie Romel, PhD, an instructor in the Department of Psychiatry at Icahn Mount Sinai and first author of the paper. "Our study does not provide evidence for a causal relationship between in-utero exposure to antidepressants and affective disorders in the child. So, while other long-term effects of intrauterine exposure to antidepressants remain to be investigated, our work supports antidepressant continuation for women with severe symptoms or a high risk of relapse because untreated psychiatric illness during pregnancy can have negative consequences on the health and development of the child. Women and their health care providers should carefully weigh all of the treatment options and jointly decide on the best course of action."
Preserving physical and mental health helps older adults experiencing cognitive impairment stave off declines in cognitive engagement, a new study suggests
“We found that declines in physical and mental health were associated with more pronounced cognitive disengagement,” says Shevaun Neupert, professor of psychology at North Carolina State University and corresponding author of the study published in Entropy.
“The impact of declines in physical health was particularly pronounced for study participants who had more advanced cognitive impairment to begin with.”
There’s a lot of research showing that cognitive engagement can help older adults maintain cognitive health. However, the vast majority of that work has been done on healthy adults.
“There’s very little work on cognitive engagement in people who are already cognitively impaired, such as people who have been diagnosed with dementia,” Neupert says. “Are they still capable of sustained cognitive engagement? What factors contribute to that engagement?”
To begin addressing those questions, the researchers enlisted 28 study participants. All of the participants were over 60 and had documented cognitive impairment.
Participants came to a testing site two times, six months apart. On each visit, researchers collected data on the physical and mental health of the study participants and performed a battery of tests designed to assess cognitive ability. They also connected participants to a device that tracked blood pressure continuously and then asked them to engage in a series of increasingly difficult cognitive tasks. This allowed researchers to track how cognitive engagement changed as the tasks become progressively harder.
Cognitive engagement means taking part in activities that are mentally challenging. Monitoring blood pressure allows the researchers to track how hard study participants are working to accomplish cognitive tasks. Specifically, blood pressure rises as more blood is pumped to the brain when participants work harder at these tasks.
Broadly speaking, the researchers found that if a participant’s cognitive ability, physical health, or mental health declined over the course of the six month study period, that participant became less cognitively engaged as the tasks became harder.
“Normally, you’d expect more engagement as the tasks became harder, but we found that some people essentially stopped trying,” says coauthor Claire Growney, a postdoctoral researcher at Washington University in St. Louis.
“The findings highlight the fact that well-being is holistic; physical health, mental health, and cognitive function can influence each other,” says coauthor Xianghe Zhu, a recent PhD graduate of NC State.
“In practical terms, it suggests that it may be particularly important for people to focus on mental and physical well-being during the early stages of cognitive decline,” Growney says. “Or, at the very least, don’t become so focused on addressing cognitive challenges that you ignore physical health, or create anxiety or emotional distress for yourself that leads to mental health problems.”
“Future research will be needed to determine how beneficial it might be for people to take part in cognitively engaging activities once they’ve started experiencing cognitive decline,” Neupert says.
“But we already know that there is an element of ‘use it or lose it’ to cognitive function in healthy adults. And while it’s understandable for people to want to avoid tasks that are difficult or challenging, it’s really important to continue challenging ourselves to take part in difficult cognitive activities.”