Anti-aging compound improves muscle glucose metabolism in people
Washington University School of Medicine in St. Louis, April 26, 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, PhD, 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.
N-acetylcysteine for depression in adolescents and young adults at risk for bipolar disorder
University of Cincinnati, April 23, 2021
According to news reporting originating from Cincinnati, Ohio, by NewsRx correspondents, research stated, “To investigate the mechanism of action of N-acetylcysteine (NAC) in depressive symptoms in young individuals at familial risk for bipolar disorder. We conducted an 8-week open label clinical trial of NAC 2400 mg/days in 15-24 years old depressed offspring of a bipolar I disorder parent, with baseline and endpoint proton magnetic resonance spectroscopy acquired within the left ventrolateral prefrontal cortex (VLPFC).”
Our news editors obtained a quote from the research from the University of Cincinnati, “Nine participants were enrolled and finished the study. NAC significantly improved depressive and anxiety symptom scores, and clinical global impression (all p< .001). There was a non-significant reduction in glutamate levels in the left VLPFC. Reduction in depressive symptom scores was positively associated with reduction in glutamate levels in the left VLPFC (p = .007).”
According to the news editors, the research concluded: “This pilot study suggests that NAC might be efficacious for depressive symptoms in at-risk youth, and that its mechanism of action involves the modulation of glutamate in the left VLPFC.”
This research has been peer-reviewed.
Soda consumption linked to accelerated aging and increased mortality risk
University of California at San Francisco, April 26, 2021
A recent study by researcher from the University of California, San Francisco says that drinking soda can increase the risk of all-cause mortality and accelerate aging. The findings build on mounting evidence of the adverse effects drinking soda and other sugary beverages have on the body, which include obesity, Type 2 diabetes, heart disease, kidney disease, non-alcoholic fatty liver disease, dental caries and gout.
The team collated data from the National Health and Examination Surveys, an annual program for assessing the health and nutrition of American adults and children. They gathered data from over 5,300 participants between 1999 and 2002, all of whom had no history of diabetes or cardiovascular disease.
In particular, they looked at stored DNA data from the participants – measuring telomere length and comparing it with their consumption of sugar-sweetened soda. The researchers found that those who regularly drank sugar-sweetened soda had shorter telomeres than those who didn’t.
Research has shown that telomeres have been previously associated with lifespan. Having shorter telomere length, for instance, has been linked to cardiovascular disease, diabetes and even certain types of cancer.
The team reported in their study that consuming even just eight ounces of soda every day can accelerate aging by nearly two years. Meanwhile, 20 ounces of soda can accelerate aging by up to 4.6 years when consumed daily. In fact, drinking sugar-sweetened soda can reduce telomere length at a rate similar to smoking.
The UCSF study is also the first to link regular consumption of sugar-sweetened soda to telomere shortening. According to study co-author Elissa Epel, drinking sugar-sweetened soda adds strain to the body by metabolizing these sugars and accelerates cellular aging in tissues.
“This finding held regardless of age, race, income and education level. Telomere shortening starts long before disease onset,” Epel added. ” Although we only studied adults here, it is possible that soda consumption is associated with telomere shortening in children, as well.”
Sugary sodas linked to rising all-cause deaths
In another study, European experts revealed that drinking sugary sodas and other sweetened drinks increases the risk of all-cause deaths. The researchers collected data from more than 450,000 individuals enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large-scale cohort study for biochemical and genetic markers for cancer and other chronic diseases.
A follow-up revealed that more than 40,000 participants from the original study had already died. Using their data, the team found a strong link between regular soda consumption and all-cause mortality. Those who regularly drank more than two glasses of sugary drinks increased their risk of dying from circulatory diseases, while those who drank at least one glass of sugary drinks increased their risk of dying from digestive diseases and Parkinson’s disease.
“Our results … provide additional support for the possible adverse health effects of sugar-sweetened soft drinks and to replace them with other healthier beverages, preferably water,” explained co-author Neil Murphy. “For artificially-sweetened soft drinks, we now need a better understanding of the mechanisms that may underlie this association and research such as ours will hopefully stimulate these efforts.”
The findings appeared in JAMA Internal Medicine.
Curcumin concoction could combat colitis: Study
Baylor University, April 25, 2021
A formula that blends curcumin and turmeric oils can prove effective against the activity and inflammatory burden of colitis, a study has determined.
Published in Nature Scientific Reports, the study identifies the efficacy of a specific curcumin preparation containing essential turmeric oils (ETO-curcumin) in reducing colitis symptoms.
These turmeric oils, aromatic-tumerones (ar-tumerones), alpha-turmerones, beta-turmerones, alpha-santalene and aromatic curcumene, appear to be responsible for an anti-inflammatory and anti-oxidant action, the study suggests.
The combination also appeared to exert higher bioactivity than stand-alone curcumin – a feature that could prove valuable in using turmeric for other intestinal conditions.
“The therapeutic benefits of turmeric can be attained at its best by combining curcumin with turmerone, an active compound derived from essential oil of turmeric,” said P.J. Kunjachan, chairman and managing director for Arjuna Natural Extracts
“This new finding provides our customers an added value for promoting their BCM-95-based formulations in an increasingly crowded curcumin market,” added Dr Benny Antony, joint managing director for Arjuna.
BCM-95 often combines curcumin with other turmeric compounds as its poor bioavailability has been cited as a barrier to its use in other disorders.
Obstacles are not limited to curcumin's chemical properties. Despite the 17 claims for its anti-inflammatory and digestive health properties, there are currently no approved health claims for curcumin in the EU.
These claims are featured on the 2000+ list of on-hold botanical claims yet to be processed by the European Food Safety Authority (EFSA).
As well as Arjuna, other manufacturers with an interest in curcumin include herbal manufacturers Sabinsa and Italian botanicals firm Indena.
Led by Dr Shusuke Toden, research associate from Baylor University in the US, the trial compared ETO-curcumin preparations against standard curcumin at three specific doses (0, 5, 25 or 50 milligrams per kilogram (mg/kg)).
These doses were administered to an animal model with induced colitis for seven days.
The research team found that ETO-curcumin improved disease activity index (DAI) dose-dependently, while the anti-inflammatory efficacy of standard curcumin remained constant.
“This suggests that ETO-curcumin may provide superior anti-inflammatory efficacy compared to standard curcumin,” the study explained.
“ETO-curcumin associated anti-inflammatory effects were particularly pronounced at higher doses.”
Further findings revealed that anti-inflammatory proteins produced included IL-10 and IL-11 as well as FOXP3, which increased in number in the colon by ETO-curcumin.
Study examines association between lifestyle patterns and BMI in early childhood
Results support obesity prevention efforts early in life
Deakin University (Australia), April 26, 2021
A new Australian study reveals that changes in lifestyle patterns were longitudinally associated with concurrent changes in body mass index (BMI) z scores, and maternal pre-pregnancy BMI, maternal dietary patterns and television viewing time are significant determinants, according to a paper published online in Obesity, The Obesity Society's (TOS) flagship journal. This is the first study that used multi-trajectory modeling to examine the longitudinal relationship between concurrent changes in lifestyle patterns and BMI z scores in early childhood.
"The findings will inform early childhood obesity prevention intervention and policy, and will be of great interest to pediatricians, researchers, policymakers and the general public," said Miaobing Zheng of the Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, in Geelong, Australia. Zheng is the corresponding author of the study.
Experts explain that longitudinal studies investigating the association between lifestyle patterns and obesity in children are scarce. An association between a healthy lifestyle pattern and lower obesity risk has, however, been previously reported in a few cross-sectional studies. In the present study, the co-occurrence of stable healthy lifestyle patterns along with a concurrent normal BMI z score trajectory of one unit from 18 to 60 months in about half of the children provides new longitudinal evidence supporting that children with healthy lifestyles were more likely to concurrently have normal BMI z score development.
Data of 439 children were used from the Melbourne Feeding Activity and Nutrition Trial (InFANT) program. This longitudinal cohort of children commenced in 2008 as a 15-month parent-focused cluster randomized controlled trial aiming to reduce obesity risk behaviors in children until 18 months. Additional follow-ups without interventions occurred for children aged 42 and 60 months. Multi-trajectory modeling identified groups of children following similar lifestyle patterns and BMI z score trajectories and multi-nomial logistic regression assessed the determinants of the trajectory groups.
Three trajectory groups of child lifestyle patterns and BMI z scores were identified and distinguished, showing a mixture of healthy and unhealthy lifestyle behaviors and BMI zscores. Compared to Groups 1 "Unhealthy lifestyle pattern, Low BMI z" and 3 "Unhealthy lifestyle pattern, High BMI z", Group 2 "Healthy lifestyle pattern, Mid BMI z" revealed the most distinctive trajectories across lifestyle patterns and BMI z scores. Group 2 comprised nearly 53 percent of children and followed a stable and low trajectory for an unhealthy lifestyle pattern characterized by energy-dense and nutrient poor discretionary food consumption and television viewing time and a high and rising trajectory for a healthy lifestyle pattern of fruit and vegetable intakes and time outdoors, along with a mean BMI z score of +1 unit over time.
Groups 1 and 3 shared similar high trajectories for an unhealthy lifestyle pattern of discretionary food consumption and television viewing time, and low trajectories for a healthy lifestyle pattern of fruit and vegetable intakes and time outdoors. The two groups however differed in BMI z score trajectories, showing stable patterns but at mean scores of 0 and +2 units, respectively. Child sex, breastfeeding duration and maternal physical activity were not associated with the identified trajectory groups.
The study's authors note that the co-occurrence of stable lifestyle patterns and BMI z score trajectories in early childhood highlight the importance of initiating lifestyle obesity prevention early in life, and such interventions could target both children and the mother. A multi-behavior approach to simultaneously target healthy diet, physical activity and sedentary behaviors could be adapted.
"Young children learn by imitating that which they see daily. There is no doubt that children copy the behaviors observed in the presence of parents: healthy and unhealthy," said Liliana Aguayo, PhD, MPH, a childhood obesity expert, TOS member and research assistant professor from the Hubert Department of Global Health at Emory University in Atlanta, Ga. "Evidence from this study highlights the importance of early childhood as a critical period for development of obesity. More research is needed to identify effective approaches to simultaneously address parent and child health behaviors." Aguayo was not associated with the research.
DDT exposure in grandmothers linked to obesity, earlier periods in granddaughters
Young women today may face increased health risks linked to breast cancer due to effects from the banned toxic pesticide lasting over three generations
University of California at Davis, April 16, 2021
In the first study to report on the health effects of exposure to a toxic environmental chemical over three human generations, a new study has found that granddaughters whose grandmothers were exposed to the pesticide DDT have higher rates of obesity and earlier first menstrual periods. This may increase the granddaughters' risk for breast cancer as well as high blood pressure, diabetes and other cardiometabolic diseases.
The research by the Public Health Institute's Child Health and Development Studies (CHDS) and the University of California at Davis was published today in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research. It suggests that effects from the pesticide DDT -- despite being banned in the U.S. nearly 50 years ago -- may contribute to the falling age of first periods and increases in obesity rates among young women today.
The study found that the risk of obesity in young adult granddaughters was 2 to 3 times greater when their grandmothers (who were not overweight) had higher levels of o,p'-DDT (a contaminant of commercial DDT) in their blood during or just after pregnancy. Granddaughters were twice as likely to have earlier first menstrual periods when their grandmothers had higher o,p'-DDT blood levels. DDT and its related chemicals, including o,p'-DDT, are known to be endocrine disrupting chemicals, compounds that can alter and interfere with natural hormones that are essential for development.
"We already know that it's nearly impossible to avoid exposures to many common environmental chemicals that are endocrine disruptors. Now our study shows for the first time in people that environmental chemicals like DDT may also pose health threats to our grandchildren," said Barbara Cohn, director of CHDS and senior author of the study. "In combination with our on-going studies of DDT effects in the grandmother's and mother's generations, our work suggests we should take precautionary action on the use of other endocrine disrupting chemicals, given their potential to affect generations to come in ways we cannot anticipate today."
The Child Health and Development Studies is a unique project that has followed 20,000 pregnant women and their families for more than 60 years. CHDS enrolled and began following pregnant women in the Bay Area between 1959 and 1967, a time of high pesticide use before DDT was banned in 1972. These "founding grandmothers" in the study gave blood samples at each trimester during pregnancy and one sample shortly after birth. The blood samples were tested for levels of DDT and its related chemicals, including active ingredients, contaminants and their metabolites. The study today focused on o,p'-DDT as it has previously been linked to breast cancer, obesity and other harmful health effects in daughters, and is believed to be the most sensitive biomarker for exposures before and immediately after birth. Since granddaughters' exposure would occur via their mothers' in utero egg cell development, o,p'-DDT levels are a potential predictor of granddaughters' exposure outcomes.
"These data suggest that the disruption of endocrine systems by DDT initiates in immature human eggs, decades before the eggs are fertilized," said Michele La Merrill, associate professor at UCD who was co-lead author of the study.
The CHDS study included interviews, home visits and questionnaires from the daughters and granddaughters of the original enrollees. During home visits, blood pressure and height and weight measurements were taken. The study today is based on 365 adult granddaughters who completed questionnaires, participated in a home visit, had available DDT measures from grandmothers' serum, and (for 285 of them) had available information on body mass index (BMI) in all three generations. Information on the age of first period for all three generations was available from 235 granddaughters.
Previous CHDS studies have shown that mothers' DDT exposure during pregnancy or immediately after birth correlates with increased daughters' risk of breast cancer and the prevalence of breast cancer risk factors, including obesity, among adult daughters. Other prior studies have linked DDT exposure to birth defects, reduced fertility and an increased risk of diabetes.
A commentary in the journal Reproductive Toxicology last year called CHDS "a national treasure that keeps on giving" and noted that "There are no other U.S. studies as well defined, sampled, and followed as the CHDS....The CHDS provides unique and essential value in understanding health effects of environmental exposures as they relate to life-stage sensitivity."
Capsaicin analog could help treatment-resistant lung cancer
Small cell lung cancer cells exposed to synthetic analog of chili pepper compound responded better to chemotherapy
Marshall University, April 27, 2021
A new study found that non-pungent synthetic analog of capsaicin -- the compound that makes chili peppers hot -- made small cell lung cancer cells more responsive to treatment. Small cell lung cancer is a very aggressive form of cancer with a low survival rate.
Cisplatin-based combination chemotherapy is typically the first-line treatment for small cell lung cancer patients. Although patients initially respond very well to this chemotherapy, the tumor usually comes back within a year in a form that doesn't respond to treatments. Patients with relapsed small cell lung cancer have very few treatment options.
"Irinotecan is the only FDA approved second-line drug for small cell lung cancer, but less than 3% of patients respond to it," said research team leader Piyali Dasgupta, PhD, from Marshall University. "Therefore, agents that improve the anti-cancer activity of irinotecan would be of great value to these patients."
Jamie Friedman, a former doctoral student in Dasgupta's lab will present the new findings at the American Society for Investigative Pathology annual meeting during the virtual Experimental Biology (EB) 2021 meeting, to be held April 27-30.
The natural compound capsaicin has been shown to have anti-cancer effects, but its heat can also cause a burning sensation, stomach cramps, gut pain and nausea. In the new work, the researchers studied arvanil, a synthetic capsaicin analog without capsaicin's undesirable side effects.
When the researchers exposed two cisplatin-resistant lung cancer cell lines to a low concentration of arvanil, they saw no growth-inhibitory activity. However, when they treated the cells with varying concentrations of SN38 -- the active ingredient irinotecan -- they observed that the presence of arvanil greatly enhanced the ability of SN38 to slow cancer cell growth. Statistical analysis showed that the interaction between arvanil and SN38 was synergistic in nature.
"Because arvanil enhanced the anti-cancer activity of SN38 in human small cell lung cancer cells, arvanil-based combination therapies may be useful for patients with relapsed small cell lung cancer cells," said Friedman. "We hope that this work will pave the way for novel therapies for relapsed and cisplatin-resistant small cell lung cancer."
