By Jess Miller -  jenreviews.com

Psidium guajavaLinn. (guava) is used not only as food but also as folk medicine in subtropical areas around the world because of its pharmacologic activities. In particular, the leaf extract of guava has traditionally been used for the treatment of diabetes in East Asia and other countries. Moreover, the anti-hyperglycemic activity of the extract has been reported in some animal models. However, little is known regarding the therapeutic activity of the extract in human clinical trials as well as its underlying therapeutic mechanisms and safety. In Japan, Guava Leaf Tea (Bansoureicha^®, Yakult Honsha, Tokyo, Japan) containing the aqueous leaf extract from guava has been approved as one of the Foods for Specified Health Uses and is now commercially available. This review describes the active component of the aqueous guava leaf extract and its inhibition of alpha-glucosidase enzymes in vitro, safety of the extract and Guava Leaf Tea, reduction of postprandial blood glucose elevation, and improvement of hyperglycemia, hyperinsulinemia, hypoadiponectinemia, hypertriglycemia and hypercholesterolemia in murine models and several clinical trials. It is suggested that the chronic suppression of postprandial blood glucose elevation is important in preventing type 2 diabetes mellitus, and that Guava Leaf Tea is considered useful as an alimentotherapy for chronic treatment.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2831039/

Long prized as a malleable, conductive metal used in cookware, electronics, jewelry and plumbing, copper has been gaining increasing attention over the past decade for its role in certain biological functions. It has been known that copper is needed to form red blood cells, absorb iron, develop connective tissue and support the immune system.

The new findings, to appear in the July print issue of Nature Chemical Biology but published online today, establishes for the first time copper's role in fat metabolism.

The team of researchers was led by Chris Chang, a faculty scientist at Berkeley Lab's Chemical Sciences Division, a UC Berkeley professor of chemistry and a Howard Hughes Medical Institute investigator. Co-lead authors of the study are Lakshmi Krishnamoorthy and Joseph Cotruvo Jr, both UC Berkeley postdoctoral researchers in chemistry with affiliations at Berkeley Lab.

"We find that copper is essential for breaking down fat cells so that they can be used for energy," said Chang. "It acts as a regulator. The more copper there is, the more the fat is broken down. We think it would be worthwhile to study whether a deficiency in this nutrient could be linked to obesity and obesity-related diseases."

Dietary copper

Chang said that copper could potentially play a role in restoring a natural way to burn fat. The nutrient is plentiful in foods such as oysters and other shellfish, leafy greens, mushrooms, seeds, nuts and beans.

According to the Food and Nutrition Board of the Institute of Medicine, an adult's estimated average dietary requirement for copper is about 700 micrograms per day. The Food and Nutrition Board also found that only 25 percent of the U.S. population gets enough copper daily.

"Copper is not something the body can make, so we need to get it through our diet," said Chang. "The typical American diet, however, doesn't include many green leafy vegetables. Asian diets, for example, have more foods rich in copper."

But Chang cautions against ingesting copper supplements as a result of these study results. Too much copper can lead to imbalances with other essential minerals, including zinc.

Copper as a 'brake on a brake'

The researchers made the copper-fat link using mice with a genetic mutation that causes the accumulation of copper in the liver. Notably, these mice have larger than average deposits of fat compared with normal mice.

The inherited condition, known as Wilson's disease, also occurs in humans and is potentially fatal if left untreated.

Analysis of the mice with Wilson's disease revealed that the abnormal buildup of copper was accompanied by lower than normal lipid levels in the liver compared with control groups of mice. The researchers also found that the white adipose tissue, or white fat, of the mice with Wilson's disease had lower levels of copper compared with the control mice and correspondingly higher levels of fat deposits.

They then treated the Wilson's disease mice with isoproterenol, a beta agonist known to induce lipolysis, the breakdown of fat into fatty acids, through the cyclic adenosine monophosphate (cAMP) signaling pathway. They noted that the mice with Wilson's disease exhibited less fat-breakdown activity compared with control mice.

The results prompted the researchers to conduct cell culture analyses to clarify the mechanism by which copper influences lipolysis. The researchers used inductively coupled plasma mass spectroscopy (ICP-MS) equipment at Berkeley Lab to measure levels of copper in fat tissue.

They found that copper binds to phosphodiesterase 3, or PDE3, an enzyme that binds to cAMP, halting cAMP's ability to facilitate the breakdown of fat.

"When copper binds phosphodiesterase, it's like a brake on a brake," said Chang. "That's why copper has a positive correlation with lipolysis."

Hints from cows

The connection between copper and fat metabolism is not altogether surprising. The researchers actually found hints of the link in the field of animal husbandry.

"It had been noted in cattle that levels of copper in the feed would affect how fatty the meat was," said Chang. "This effect on fat deposits in animals was in the agricultural literature, but it hadn't been clear what the biochemical mechanisms were linking copper and fat."

The new work builds upon prior research from Chang's lab on the roles of copper and other metals in neuroscience. In support of President Barack Obama's BRAIN Initiative, Berkeley Lab provided Chang seed funding in 2013 through the Laboratory Directed Research and Development program. Chang's work continued through the BRAIN Tri-Institutional Partnership, an alliance with Berkeley Lab, UC Berkeley and UC San Francisco.

Of the copper in human bodies, there are particularly high concentrations found in the brain. Recent studies, including those led by Chang, have found that copper helps brain cells communicate with each other by acting as a brake when it is time for neural signals to stop.

While Chang's initial focus was on the role of copper in neural communications, he branched out to investigations of metals in fat metabolism and other biological pathways. This latest work was primarily funded by the National Institutes of Health.

Story Source:

Materials provided by DOE/Lawrence Berkeley National Laboratory. Note: Content may be edited for style and length.

Journal Reference:

1. Lakshmi Krishnamoorthy, Joseph A Cotruvo, Jefferson Chan, Harini Kaluarachchi, Abigael Muchenditsi, Venkata S Pendyala, Shang Jia, Allegra T Aron, Cheri M Ackerman, Mark N Vander Wal, Timothy Guan, Lukas P Smaga, Samouil L Farhi, Elizabeth J New, Svetlana Lutsenko, Christopher J Chang. Copper regulates cyclic-AMP-dependent lipolysis. Nature Chemical Biology, 2016; DOI: 10.1038/nchembio.2098

https://www.sciencedaily.com/releases/2016/06/160606200439.htm

"We found that all forms and sources of folate were associated with lower risk of colorectal cancer," said Victoria Stevens, PhD, of the American Cancer Society and lead author of this study. "The strongest association was with total folate, which suggests that total folate intake is the best measure to define exposure to this nutrient because it encompasses all forms and sources." Total folate includes naturally occurring food folate and folic acid from fortified foods and dietary supplements.

A research team investigated the association between folate intake and colorectal cancer among 99,523 participants in the Cancer Prevention Study II Nutrition Cohort; a total of 1,023 participants were diagnosed with colorectal cancer between 1999 and 2007, a period entirely after folate fortification began. Neither higher nor lower risk was observed during the first two years of follow-up (1999 to 2001), while associations were statistically significantly inverse for the subsequent years (2002 to 2007).

The findings of this study add to the epidemiologic evidence that high folate intake reduces colorectal cancer incidence. Further, one important difference between the current study and previous studies was the separate assessment of natural folates and folic acid. Previous studies that discriminated between folates considered only the source (i.e., diet versus supplement) and not the chemical form.

The study also addressed concerns that the intake of high levels of folate frequently consumed in the U.S. -- as a result of the recent increase in the use of folate-containing supplements and mandatory folate fortification of food -- may actually increase risk of cancer. No increased risk of colorectal cancer was found for the highest intake levels, suggesting that the high levels of this vitamin consumed by significant numbers of Americans should not lead to increased incidence rates of this cancer in the population.

Folates are essential nutrients needed to make components used for functions required for normal cell growth, including DNA synthesis and repair. Because these processes are critical for cell growth and differentiation, the relationship between folate intake and cancer development has been investigated in several cancers, and most extensively in colorectal cancer.

Story Source:

Materials provided by American Gastroenterological Association. Note: Content may be edited for style and length.

Journal Reference:

1. Victoria L. Stevens, Marjorie L. McCullough, Juzhong Sun, Eric J. Jacobs, Peter T. Campbell, Susan M. Gapstur. High Levels of Folate From Supplements and Fortification Are Not Associated With Increased Risk of Colorectal Cancer. Gastroenterology, 2011; DOI: 10.1053/j.gastro.2011.04.004

https://www.sciencedaily.com/releases/2011/07/110705123616.htm

Since the late 1980s, the prevalence of childhood elevated blood pressure has increased in the United States, in particular among African Americans. From a life course perspective, childhood high blood pressure can predict higher blood pressure values later in life, and people with higher blood pressure are at greater risk of developing cardiovascular, metabolic and kidney disease and stroke. Research has also shown that maternal cardiometabolic risk factors during pregnancy -- including hypertensive disorders, diabetes, and obesity -- are associated with higher offspring blood pressure.

Because controlling hypertension and cardiovascular disease in adults is difficult and expensive, identifying early-life factors for the prevention of high blood pressure may be an important and cost effective public health strategy.

There is growing evidence that maternal nutrition during pregnancy, through its impact on the fetal intrauterine environment, may influence offspring cardiometabolic health. Folate, which is involved in nucleic acid synthesis, gene expression, and cellular growth, is particularly important.

In young adults, higher folic acid intake has been associated with a lower incidence of hypertension later in life. Citrus juices and dark green vegetables are good sources of folic acid. However, the role of maternal folate levels, alone or in combination with maternal cardiometabolic risk factors on child blood pressure has not been examined in a prospective birth cohort.

In the current study, researchers analyzed the data from a prospective U.S. urban birth cohort, enriched by low-income racial and ethnic minorities at high risk for elevated BP, to examine whether maternal folic acid levels and cardiometabolic risk factors individually and jointly affect offspring blood pressure.

Researchers included 1290 mother-child pairs, 67.8% of which were Black and 19.2% of which were Hispanic, recruited at birth and followed prospectively up to age 9 years from 2003 to 2014 at the Boston Medical Center. Of the mothers, 38.2% had one or more cardiometabolic risk factors; 14.6% had hypertensive disorders, 11.1% had diabetes, and 25.1% had pre-pregnancy obesity. A total of 28.7% of children had elevated systolic blood pressure at age 3-9 years. Children with higher systolic blood pressure were more likely to have mothers with pre-pregnancy obesity, hypertensive disorders, and diabetes. Children with elevated systolic blood pressure were also more likely to have lower birth weight, lower gestational age, and higher BMI.

The study findings suggest that higher levels of maternal folic acid may help counteract the adverse associations of maternal cardiometabolic risk factors with child systolic blood pressure, although maternal folic acid levels alone were not associated with child systolic blood pressure. Among children born to mothers with any of the cardiometabolic risk factors, those whose mothers had folic acid levels above the median had 40% lower odds of elevated childhood systolic blood pressure. These associations did not differ appreciably in analyses restricted to African Americans, and they were not explained by gestational age, size at birth, child postnatal folate levels or breastfeeding.

"Our study adds further evidence on the early life origins of high blood pressure," said Dr. Xiaobin Wang, the study's senior corresponding author. "Our findings raise the possibility that early risk assessment and intervention before conception and during pregnancy may lead to new ways to prevent high blood pressure and its consequences across lifespan and generations."

Story Source:

Materials provided by Oxford University Press USA. Note: Content may be edited for style and length.

Journal Reference:

1. Hongjian Wang, Noel T. Mueller, Jianping Li, Ninglin Sun, Yong Huo, Fazheng Ren, Xiaobin Wang. Association of Maternal Plasma Folate and Cardiometabolic Risk Factors in Pregnancy with Elevated Blood Pressure of Offspring in Childhood. American Journal of Hypertension, 2017; DOI: 10.1093/ajh/hpx003

https://www.sciencedaily.com/releases/2017/03/170308081047.htm

The research, published August 11 in the journal Science, is important because it identifies a potential therapeutic target for rebalancing gut microbiota and adds to a growing body of knowledge on the complex interplay between gut microbiota and dietary fiber.

An accompanying Insights / Perspectives article in the same issue of the journal describes gut microbes as "partners" in the body's defense against potential infectious agents, such as Salmonella.

"Our research suggests that one of the best approaches to maintaining gut health might be to feed the beneficial microbes in our intestines dietary fiber, their preferred source of sustenance," said Andreas Bäumler, professor of medical microbiology and immunology at UC Davis Health and senior author of the study.

"While it is known that the gut is the site of constant turf wars between microbes, our research suggests that signals generated by beneficial microbes drive the intestinal tract to limit resources that could lead to an expansion of potentially harmful microbes," he said.

Resident gut microbes metabolize indigestible dietary fiber to produce short-chain fatty acids, which signal cells lining the large bowel to maximize oxygen consumption, thereby limiting the amount of oxygen diffusing into the gut lumen (the open space within the intestine that comes into direct contact with digested food.)

"Interestingly, the beneficial gut bacteria that are able to breakdown fiber don't survive in an environment rich in oxygen, which means that our microbiota and intestinal cells work together to promote a virtuous cycle that maintains gut health," Mariana X. Byndloss, assistant project scientist and first author on the study.

The new research identified the host receptor peroxisome proliferator receptor gamma (PPARg) as the regulator responsible for maintaining this cycle of protection.

"When this host signaling pathway malfunctions, it leads to increased oxygen levels in the gut lumen," Bäumler said. "These higher oxygen levels make us more susceptible to aerobic enteric pathogens such as Salmonella or Escherichia coli, which use oxygen to edge out competing beneficial microbes."

Story Source:

Materials provided by University of California - Davis Health System. Note: Content may be edited for style and length.

Journal Reference:

1. Mariana X. Byndloss, Erin E. Olsan, Fabian Rivera-Chávez, Connor R. Tiffany, Stephanie A. Cevallos, Kristen L. Lokken, Teresa P. Torres, Austin J. Byndloss, Franziska Faber, Yandong Gao, Yael Litvak, Christopher A. Lopez, Gege Xu, Eleonora Napoli, Cecilia Giulivi, Renée M. Tsolis, Alexander Revzin, Carlito B. Lebrilla, Andreas J. Bäumler. Microbiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion. Science, 2017 DOI: 10.1126/science.aam9949

https://www.sciencedaily.com/releases/2017/08/170810173334.htm

Dozens of animal studies using different animal species have found that vitamin C significantly prevents and alleviates infections caused by diverse bacteria, viruses, and protozoa. Given the universal nature of the effect of vitamin C against various infections in different animal species, it also seems evident that vitamin C influences the susceptibility to, and the severity of infections in humans. However, the practical importance of vitamin C in human infections is not known.

"Maternal nutrition during pregnancy can have long-lasting effects on child health, as well as the health of a mother after pregnancy," said the study's principal investigator, Xiaobin Wang, M.D., M.P.H., Sc.D., from Johns Hopkins University, Baltimore. "Our results suggest that adequate maternal folate may mitigate the effect of a mother's obesity on her child's health."

The study, published online in JAMA Pediatrics, was funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

Obesity in children and adults is a serious health issue in the United States, contributing to such conditions as heart disease, stroke and type 2 diabetes. During pregnancy, maternal obesity also increases the risk for a range of pregnancy complications, such as stillbirth, birth defects and preterm birth. Furthermore, babies born to obese mothers have long-term health risks, including a higher risk of obesity in childhood.

Folate, an essential B vitamin, reduces the fetus' risk for neural tube defects, which are malformations affecting the brain, spine and spinal cord. The U.S. Centers for Disease Control and Prevention recommends that women of childbearing age take 400 micrograms of folic acid (a synthetic form of folate) daily to reduce their children's risk for neural tube defects. However, the role of maternal folate levels on a child's future obesity risk was not known, especially among those born to mothers who are obese during pregnancy.

In their study, the researchers investigated the health outcomes of mothers and children (ranging from 2- to 9-years-old) in the Boston Birth Cohort, a predominately low-income, minority population with a high prevalence of maternal and child obesity. The study team analyzed health records from more than 1,500 mother-child pairs, including information that was collected before, during and after pregnancy. To gauge a mother's folate level during pregnancy, the researchers measured folate from stored plasma samples that were collected two to three days after delivery.

The study team found a wide range of maternal folate levels, but observed an "L-shaped" relationship between maternal folate levels and child obesity. In other words, the lowest levels of folate correlated with the highest risk of child obesity. When folate levels reached approximately 20 nanomoles per liter (nm/L), which is within the normal range for adults, further increases in folate levels did not confer additional benefits, indicating a threshold or ceiling effect.

According to the researchers, this threshold is higher than the standard cutoff for diagnosing folate deficiency (less than 10 nm/L).

Obese mothers in the study tended to have lower folate levels than normal weight mothers. However, when the researchers examined obese mothers only, they found that children of obese mothers with adequate folate levels (at least 20 nm/L) had a 43 percent lower risk of obesity compared to children of obese mothers with lower folate (less than 20 nm/L). The children in the latter group had higher body mass index-for-age z-scores (BMI-z)--a measure of body fat in children.

According to the authors, establishing an "optimal" rather than "minimal" folate concentration may be beneficial for women planning a pregnancy, especially obese women.

"Folate is well-known for preventing brain and spinal cord defects in a developing fetus, but its effects on metabolic disorders, such as diabetes and obesity, is less understood," said Cuilin Zhang, M.D., Ph.D., NICHD senior investigator and a study co-author. "This study uncovers what may be an additional benefit of folate and identifies a possible strategy for reducing childhood obesity."

Story Source:

Materials provided by NIH/Eunice Kennedy Shriver National Institute of Child Health and Human Development. Note: Content may be edited for style and length.

Journal Reference:

1. Wang G, Hu FB, Mistry KB, Zhang C, Ren F, Huo Y, Paige D, Bartell T, Hong X, Caruso D, Ji Z, Chen Z, Ji Y, Pearson C, Ji H, Zuckerman B, Cheng TL, and Wang X. Associations of maternal prepregnancy BMI and plasma folate concentrations with child metabolic health. JAMA Pediatrics, June 2016 DOI: 10.1001/jamapediatrics.2016.0845

https://www.sciencedaily.com/releases/2016/06/160613122220.htm

In the Proceedings of the National Academy of Sciences, the researchers described a branching point in the metabolic pathway for vitamin A that hinges on a single protein, called ISX. The pathway starts with beta-carotene -- the pigmented nutrient that gives sweet potatoes and carrots their color. Beta-carotene forms vitamin A in the small intestine. From there, the majority of vitamin A is transported to other tissues to support healthy vision and other functions. Some vitamin A is also used to produce a growth factor for immune cells in the gut. By studying mice genetically modified to lack ISX, the researchers found ISX helps the body balance this process.