Study finds effectiveness of fasting diet (5:2 diet) in clearing fat

Researchers from the University of Surrey examined the effectiveness of the 5:2 diet vs. daily calorie restriction diet. They found that 5:2 diet clears triglycerides from blood quicker after eating meals. Their findings are published in British Journal of Nutrition reports.

The study divided overweight people into two groups. One group was assigned 5:2 diet another group was assigned daily calorie restriction diet. They measured days required for 5% weight loss, ability to clear fat and glucose from the blood. The 5:2 diet involved eating regularly for five days and restricting remaining 2 days to 600 calories per day.

Results of the study showed that subjects assigned to 5:2 diet lost 5% weight in 59 days compared other group which took 73 days. Researchers also found improved ability to clear triglycerides in this group. The study also found 9% reduction in systolic blood pressure by in 5:2 group.

Dr. Rona Antoni, Research Fellow in Nutritional Metabolism at the University of Surrey, said:

As seen in this study, some of our participants struggled to tolerate the 5:2 diet, which suggests that this approach is not suited to everybody; ultimately the key to dieting success is finding an approach you can sustain long term.

“But for those who do well and are able stick to the 5:2 diet, it could potentially have a beneficial impact on some important risk markers for cardiovascular disease, in some cases more so than daily dieting. However, we need further studies to confirm our findings, to understand the underlying mechanisms and to improve the tolerability of the 5:2 diet.”

Citation:  Antoni, Rona, Kelly L. Johnston, Adam L. Collins, and M. Denise Robertson. “Intermittent v. Continuous Energy Restriction: Differential Effects on Postprandial Glucose and Lipid Metabolism following Matched Weight Loss in Overweight/obese Participants.” British Journal of Nutrition 119, no. 05 (2018): 507-16. doi:10.1017/s0007114517003890.

Adapted from press release by the University of Surrey.

Research in mice show antioxidants in blue maize have protective effect against metabolic syndrome

A new study shows that a rat model of metabolic syndrome fed a high-sugar and high-cholesterol diet and given blue maize extract showed significant improvement in systolic blood pressure, high density lipoprotein (HDL) cholesterol, and triglyceride levels compared to those not given the extract. The natural antioxidants present in blue maize may help protect against metabolic syndrome, cardiovascular disease, diabetes, and cancer, raising interest in using blue maize as a component of functional foods and nutraceuticals, according to an article published in Journal of Medicinal Food.

Credit: Pexels /Pixabay

In the article Rosa Isela Guzman-Geronimoa and coauthors from Universidad Veracruzana, Instituto Tecnologico de Veracruz, and Unidad Oaxaca/Calle Hornos, Mexico, report that the animals fed a high-sugar and high-cholesterol diet that received blue maize extract had a significantly smaller increase in abdominal fat compared to the abdominal fat gain in rats that did not receive the extract.

“Anti-obesity food materials are always in demand, and this study brings out not only the importance of blue maize in controlling adipocity, but also the potential role of cholesterol in the development of obesity,” says Journal of Medicinal Food Editor-in-Chief Sampath Parthasarathy, MBA, PhD, Florida Hospital Chair in Cardiovascular Sciences and Interim Associate Dean, College of Medicine, University of Central Florida.

Citation: Guzmán-Gerónimo Rosa Isela, Alarcón-Zavaleta Tania Margarita, Oliart-Ros Rosa María, Meza-Alvarado José Enrique, Herrera-Meza Socorro, and Chávez-Servia José Luis. “Blue Maize Extract Improves Blood Pressure, Lipid Profiles, and Adipose Tissue in High-Sucrose Diet-Induced Metabolic Syndrome in Rats.” Journal of Medicinal Food. December 2016, ahead of print. DOI:10.1089/jmf.2016.0087

Research shows red cabbage microgreens reduce weight gain and lower cholesterol in mice fed on high-fat diet

Microgreens are sprouting up everywhere from upscale restaurants to home gardens. They help spruce up old recipes with intense flavors and colors and are packed with nutrients. Now research has shown that for mice on a high-fat diet, red cabbage microgreens helped lower their risk factors for developing cardiovascular disease and reduce their weight gain. The report appears in ACS’ Journal of Agricultural and Food Chemistry.

In an animal study, red cabbage microgreens helped lower “bad” cholesterol. Credit: American Chemical Society

Microgreens are tender, immature plants and herbs that take only a week or two to grow before they’re ready for harvesting. A growing body of research suggests that microgreens could offer more health benefits than their mature counterparts. And since previous studies have shown that full-grown red cabbage can help guard against excessive cholesterol, Thomas T.Y. Wang and colleagues wanted to see if red cabbage microgreens might have a similar or even greater effect than their larger counterparts.

To test their hypothesis, the researchers used mice that were a modelled for obesity. These animals also tend to develop high cholesterol and other risk factors for cardiovascular disease. The team divided 60 of these mice into different diet groups. They received food low in fat or high in fat, and with or without either red cabbage microgreens or mature red cabbage. Both the microgreens and mature cabbage diets reduced weight gain and levels of liver cholesterol in the mice on high-fat diets. The study showed that microgreens intake lowered LDL cholesterol, liver triglyceride, and inflammatory cytokine levels in the animals. 

Citation: Huang, Haiqiu, Xiaojing Jiang, Zhenlei Xiao, Lu Yu, Quynhchi Pham, Jianghao Sun, Pei Chen, Wallace Yokoyama, Liangli Lucy Yu, Yaguang Sunny Luo, and Thomas T. Y. Wang. “Red cabbage microgreen lower circulating LDL, liver cholesterol and inflammatory cytokines in mice fed a high fat diet.” Journal of Agricultural and Food Chemistry (2016).
DOI: 10.1021/acs.jafc.6b03805
Research funding: U.S. Department of Agriculture.
Adapted from press release by The American Chemical Society.

Research shows Statins lower the risk of Alzheimer’s disease

The new study shows that, based on a sample of 399,979 Medicare beneficiaries, men and women who took statins two years or more lowered their risk of Alzheimer’s disease in the period spanning from 2009 to 2013. The incidence of Alzheimer’s disease was reduced for beneficiaries frequently prescribed statins (high users), compared to low users, USC and University of Arizona researchers found. Among women who were high users, the incidence rate was 15 percent lower. Among men, the rate was 12 percent lower.

Researchers found the risk of Alzheimer’s disease was reduced for Medicare beneficaries who were frequently prescribed statins. The risk reduction, measured by the hazard rate, varied by statin. Rates below 1 are statistically significant. Credit: USC Schaeffer Center and JAMA Neurology

Researchers noted that black men were the only group that did not show a statistically significant reduction in risk, likely due to sample size. “We may not need to wait for a cure to make a difference for patients currently at risk of the disease. Existing drugs, alone or in combination, may affect Alzheimer’s risk,” said lead and corresponding author Julie Zissimopoulos, associate director of the USC Leonard D. Schaeffer Center for Health Policy and Economics and assistant professor at USC Price School of Public Policy.

Prior studies have shown a link between cholesterol and the hallmark of Alzheimer’s disease: the beta-amyloid plaques that interfere with memory and other brain functions. “We looked to statins as a candidate because they are widely used and have resulted in the reduction of cholesterol,” she said. The findings were published in JAMA Neurology.

Although much is known about Alzheimer’s, scientists have been unsuccessful so far in developing effective treatments to prevent and slow the memory-erasing disease that affects more than 5 million Americans. Hopes were high for the experimental drug, solanezumab, by Eli Lilly that was designed to attack the amyloid plaques. The drug failed for patients with mild dementia in a recent large clinical trial.

In a previous study, Zissimopoulos found that if medical advances could delay the disease’s onset by a year, more than 2 million Americans would be spared from developing Alzheimer’s. This also would result in a $220 billion savings in health and caregiving costs by 2050. Zissimopoulos cautioned that a silver tsunami of aging baby boomers will increase the number of Alzheimer’s patients 70 and older to 9.1 million by 2050. Annual health care costs will surge to $1.5 trillion.

The research team divided the patients into two groups: high-use beneficiaries those who took statins for two years or more between 2006 and 2008 and low-use beneficiaries who took them less frequently or who started taking statins after 2008. Both sets of beneficiaries were in similar health and had no diagnosis of Alzheimer’s disease. The researchers studied records dating from 2009 to 2013 to track the onset of Alzheimer’s disease.

The estimated 400,000 Medicare beneficiaries who became the focus of the study were 65 and older as of January 2006 and were continuously enrolled in Medicare fee-for-service and Part D prescription drug coverage. The study sought results on four of the most commonly prescribed statins: simvastatin, atorvastatin, pravastatin and rosuvastatin.

The researchers also found a reduction in risk for certain demographic groups who were frequently prescribed statins for two years or more. The greatest drop in incidence of Alzheimer’s disease 29 percent was among Hispanic men. Among white men, high users of statins had an 11-percent lower risk of incidence of the disease. A similar reduction in risk  12-percent was found among Hispanic women.

The risk of Alzheimer’s disease was also lower for white women who were high users (15 percent lower than women who took statins less frequently). Simvastatin was linked to a reduced risk of Alzheimer’s for white women, Hispanic women and black women, as well as for white men and Hispanic men. Atrovastatin was associated with a reduced risk of Alzheimer’s for white women, Hispanic women, black women and Hispanic men. Pravastatin and rosuvastatin results showed a statistically significant reduction of Alzheimer’s risk for only white women.

Some scientists believe that certain statins such as atorvastatin and simvastatin, known as lipophilics, would be most effective as an Alzheimer’s preventive treatment because they cross the blood-brain barrier, a protective layer of cells that restricts the types of substances that can pass to the brain. “We generally found that they’re all associated with reduced risk,” Zissimopoulos said.

The researchers plan to study combinations of other existing drugs to measure their effects on the risk of Alzheimer’s disease.

Citation: Julie M. Zissimopoulos, Douglas Barthold, Roberta Diaz Brinton, Geoffrey Joyce. “Sex and Race Differences in the Association Between Statin Use and the Incidence of Alzheimer Disease”. JAMA Neurology 2016 vol: 111 (5) pp: 390-400.
DOI: 10.1001/jamaneurol.2016.3783
Research funding: NIH/National Institute on Aging, USC Zumberge Research Fund.

Understanding biochemical functions of Xanthohumol – a possible avenue to treat metabolic syndrome

(Corvallis) – Researchers at Oregon State University have made a fundamental advance in understanding xanthohumol – a compound found in hops that’s of significant interest to prevent or treat the lipid and metabolic disorders that are a primary killer of people in the developed world.

The scientists identified for the first time more precisely how xanthohumol works, and why it may have such significant promise in addressing the high cholesterol, blood sugar, obesity and other issues that are collectively referred to as “metabolic syndrome.”

The findings were recently published in BBA – Proteins and Proteomics, a professional journal, by researchers from several OSU departments and the Linus Pauling Institute. The work was supported in part by the National Institutes of Health.

More than 25 percent of the adults in the United States meet the criteria for metabolic syndrome, putting them at significantly increased risk for cardiovascular disease and type-2 diabetes. That syndrome is defined by diagnosis of three or more of several conditions, including abdominal obesity, elevated lipids, high blood pressure, pro-inflammatory state, a pro-thrombotic state and insulin resistance or impaired glucose tolerance.

The new research was based on mass spectrometry in combination with a chemical labeling technique. In it, the scientists concluded that several “prenylflavonoids,” particularly xanthohumol, clearly are a ligand, or have a binding mechanism that promotes the activity of the Farnesoid X Receptor, or FXR. FXR, in turn, is a master regulator of lipid and glucose metabolism – in simpler terms, the body’s processing of fats and sugar.

There’s already interest in targeting FXR as a possible approach to a therapy for fatty liver disease, type2 diabetes and obesity,” said Claudia Maier, a professor of chemistry in the OSU College of Agricultural Sciences. “With this work we’ve identified a unique binding mechanism and chemical structure that could make that possible. This is really very interesting, and very promising.”

This new understanding of the FXR receptor at the molecular level, researchers said, could, in theory, facilitate the use of compounds that take advantage of it – such as xanthohumol – or development of other compounds with a similar chemical structure that work even better.

“We now see how these prenylflavonoids are working, and with modification through computational approaches it might be possible to even improve upon that,” said Liping Yang, the lead author on the new study and faculty research assistant in the OSU Department of Chemistry. “The end result might be either supplements or a prescription drug, with the potential to address metabolic syndrome, non-alcoholic liver disease, diabetes and other metabolic disorders.”

The FXR receptor, the scientists said, is a part of normal lipid and glucose metabolism, working in collaboration with appropriate diet, weight, exercise and other healthy activities. However, its function can be eroded by intake of too much fat and sugar. Restoring that function, by contrast, may help address metabolic problems.

In previous research, published earlier this year by OSU scientists Cristobal Miranda and Fred Stevens, scientists studied laboratory animals that were on a high-fat diet. When they were given a high dosage of xanthohumol, it reduced their LDL, or “bad” cholesterol by 80 percent; their insulin level by 42 percent; and their level of IL-6, a biomarker of inflammation, by 78 percent.

Weight gain was also constrained, compared to animals not given xanthohumol. The levels of xanthohumol used in the research far exceeded any amount that could be obtained by normal dietary intake, but could be easily obtained through supplements.

In that study, researchers pointed out that direct health care costs arising from obesity or related disorders account for up to 10 percent of U.S. health care expenditures.

Publication:Conformational modulation of the farnesoid X receptor by prenylflavonoids: Insights from hydrogen deuterium exchange mass spectrometry (HDX-MS), fluorescence titration and molecular docking studies.
DOI: http://dx.doi.org/10.1016/j.bbapap.2016.08.019
Adapted from press release by Oregon State University

Glioblastoma’s dependence of cholesterol from astrocytes, a possible new therapeutic target

Researchers at University of California San Diego School of Medicine, Ludwig Institute for Cancer Research and The Scripps Research Institute, with colleagues in Los Angeles and Japan, report that depriving deadly brain cancer cells of cholesterol, which they import from neighboring healthy cells, specifically kills tumor cells and caused tumor regression and prolonged survival in mouse models.

The findings, published in the online October 13 issue of Cancer Cell, also present a potential alternative method for treating glioblastomas (GBM), the most common and most aggressive form of brain cancer. Glioblastomas are extremely difficult to treat. The median survival rate is just over 14 months, with few treated patients living five years or more past diagnosis.

Adult brain cancers are almost universally fatal, in part because of the biochemical composition of the central nervous system (CNS) and the blood-brain barrier, which selectively and protectively limits the passage of molecules from the body into the brain, but which also blocks most existing chemotherapies, contributing to treatment failure.

This includes blocking small molecule inhibitors that target growth factor receptors, which have not proven to be effective with brain cancers, possibly due to their inability to get past the blood-brain barrier and achieve sufficiently high levels in the central nervous system.

“Researchers have been thinking about ways to deal with this problem,” said senior author Paul S. Mischel, MD, a member of the Ludwig Cancer Research branch at UC San Diego and professor in the UC San Diego School of Medicine Department of Pathology. “We have been challenged by the fact that glioblastomas are among the most genomically-well characterized forms of cancer, with clear evidence of targetable driver oncogene mutations but this information has yet to benefit patients, at least in part, because the drugs designed to target these oncogenes have difficulty accessing their targets in the brain. We have been trying to find an alternative way to use this information to develop more effective treatments.

“One such approach stems from the observation that oncogenes (mutated genes) can rewire the biochemical pathways of cells in ways that make them dependent on proteins that are not themselves encoded by oncogenes. Targeting these ‘oncogene-induced co-dependencies’ opens up a much broader pharmacopeia, including the use of drugs that aren’t traditionally part of cancer drug pipelines but have better pharmacological properties.”

In previous research, Mischel and others had noted glioblastoma cells cannot synthesize cholesterol, which is vital to cell structure and function, particularly in the brain. Instead, glioblastoma cells derive what they need from brain cells called astrocytes, which produce cholesterol in abundance. Roughly 20 percent of total body cholesterol is found in the brain.

When normal cells have sufficient cholesterol, they convert some of it into molecules called oxysterols, which activate a receptor in the cell’s nucleus — the liver X receptor (LXR) — to shut down the uptake of cholesterol.

“So when normal cells get enough cholesterol, they stop making it, stop taking it up and start pumping it out,” said Mischel. “We found that in glioblastoma cells, this mechanism is completely disrupted. They’re like parasites of the brain’s normal cholesterol system. They steal cholesterol and don’t have an off switch. They just keep gobbling the stuff up.”

Glioblastoma cells ensure their cholesterol supply by suppressing the production of oxysterols, the researchers said, ensuring cells’ LXRs remain inactive.

The research team, including Andrew Shaiu and Tim Gahman of Ludwig’s Small Molecule Development team at UC San Diego, identified an experimental metabolic disease drug candidate named LXR-623 that activates LXRs.

In mouse models, LXR-623 easily crossed the blood-brain barrier to bind with LXRs in normal cells, stimulating the production of oxysterols and the reduction of cholesterol. There was no effect upon healthy neurons and other brain cells, the scientists found, but glioblastoma cells were deprived of vital cholesterol, resulting in cell death and tumor regression.

“Disrupting cholesterol import by glioblastoma cells caused dramatic cancer cell death and shrank tumors significantly, prolonging the survival of the mice,” said Mischel. “The strategy worked with every single glioblastoma tumor we looked at and even on other types of tumors that had metastasized to the brain. LXR-623 also had minimal effect on astrocytes or other tissues of the body.”

Mischel suggested the glioblastoma strategy could be implemented in clinical trials using drug-candidates under development or in early trials.

Publication: An LXR-Cholesterol Axis Creates a Metabolic Co-Dependency for Brain Cancers.
DOI: http://dx.doi.org/10.1016/j.ccell.2016.09.008
Adapted from press release by University of California, San Diego, and Ludwig Institute for Cancer Research.