Low carbohydrate diet can increase risk of premature death, finds study

Low carbohydrate diets are unsafe and should be avoided, according to a large study presented today at ESC Congress 2018.

Study author Professor Maciej Banach, of the Medical University of Lodz, Poland, said: "We found that people who consumed a low carbohydrate diet were at greater risk of premature death. Risks were also increased for individual causes of death including coronary heart disease, stroke, and cancer. These diets should be avoided."

Obesity is a major health issue worldwide and raises the risk of several chronic conditions, including cardiovascular disease, hypertension, type 2 diabetes, and cancer. Different diets have been suggested for weight loss, such as diets low in carbohydrates and high in protein and fat. The long-term safety of these diets is controversial, with previous studies reporting conflicting results of their influence on the risk of cardiovascular disease, cancer, and death.

This study prospectively examined the relationship between low carbohydrate diets, all-cause death, and deaths from coronary heart disease, cerebrovascular disease (including stroke), and cancer in a nationally representative sample of 24,825 participants of the US National Health and Nutrition Examination Survey (NHANES) during 1999 to 2010. Compared to participants with the highest carbohydrate consumption, those with the lowest intake had a 32% higher risk of all-cause death over an average 6.4-year follow-up. In addition, risks of death from coronary heart disease, cerebrovascular disease, and cancer were increased by 51%, 50%, and 35%, respectively.

The results were confirmed in a meta-analysis of seven prospective cohort studies with 447,506 participants and an average follow-up 15.6 years, which found 15%, 13%, and 8% increased risks in total, cardiovascular, and cancer mortality with low (compared to high) carbohydrate diets (see figure for total mortality).

Professor Banach said: "Low carbohydrate diets might be useful in the short term to lose weight, lower blood pressure, and improve blood glucose control, but our study suggests that in the long-term they are linked with an increased risk of death from any cause, and deaths due to cardiovascular disease, cerebrovascular disease, and cancer."

Participants in the NHANES study had an average age of 47.6 years, and 51% were women. They were divided into quartiles based on the usual percentage of carbohydrates in their diet. The risks of all-cause and cause-specific death over an average 6.4-year follow-up rose with each fall in carbohydrate intake (see table), and remained significant after adjusting for all available factors that might have influenced the association (model 2 in the table).

The researchers also examined the link between all-cause death and low carbohydrate diets for obese (body mass index [BMI] 30 kg/m2 or greater) and non-obese (BMI under 30 kg/m2) participants in two age groups (55 years and older versus under 55) and found that the link was strongest in the non-obese older participants.

Low carbohydrate diet can increase risk of premature death, finds study

Overdose risk increases five-fold with concurrent opioid and benzodiazepine use

In continuation of my update on benzodiazepine

In the first 90 days of concurrent opioid and benzodiazepine use, the risk of opioid-related overdose increases five-fold compared to opioid-only use among Medicare recipients, according to a new study from the University of Pittsburgh School of Pharmacy, published today in JAMA Network Open.

The U.S. Centers for Disease Control and Prevention recommends against concurrent use of opioids and benzodiazepines, but nearly a quarter of Medicare recipients who are prescribed opioids also fill prescriptions for benzodiazepines. Both drugs have sedative effects.

"Patients who must be prescribed both an opioid and a benzodiazepine should be closely monitored by health care professionals due to an increased risk for overdose, particularly in the early days of this medication regimen," said Inmaculada Hernandez, Pharm.D., Ph.D., assistant professor at Pitt's School of Pharmacy and the study's lead author. "Moving forward, policy interventions should focus on preventing concurrent exposure instead of simply reducing the length of time patients use both drugs."

Hernandez and her team used 2013-2014 Medicare Part D data to assess how the duration of simultaneous exposure to the two types of drugs impacts the risk of overdose. Beneficiaries not being treated for cancer who filled at least one opioid prescription during that year were included in the analysis, which ultimately looked at more than 71,000 beneficiaries who averaged 66.5 years of age.

Patients were divided into two groups, those with a supply of only opioids the day before an overdose, and those with an opioid and benzodiazepine supply. The second group was then divided into four subgroups based on the cumulative number of days with overlapping opioid and benzodiazepine supplies.

For patients who did not have an overdose event in the first 90 days of concurrent use, overdose risk in the next 90 days decreased from five-fold to less than double, which is still elevated compared to opioid-only use. After 180 days of concurrent use, the risk of overdose was no higher than the risk for opioid-only use.

Results were adjusted to account for patient demographics, health insurance factors, clinical characteristics, and the number of unique clinicians who prescribed opioids or benzodiazepines to the patients.

Hernandez and her team also found that a beneficiary's risk of concurrent opioid and benzodiazepine use and of overdose increased with the numbers of opioid and benzodiazepine prescribers. In other words, the more clinicians prescribing medications to a beneficiary, the higher the risk of that beneficiary overdosing.

"These findings demonstrate that fragmented care plays a role in the inappropriate use of opioids, and having multiple prescribers who are not in communication increases the risk for overdose," said Yuting Zhang, Ph.D., director, Pharmaceutical Economics Research Group, Health Policy and Management, Pitt Graduate School of Public Health, and the study's senior author. "Prescription monitoring programs and policy interventions can help curb this problem and reduce risk for patients."

Overdose risk increases five-fold with concurrent opioid and benzodiazepine use

Clinical trial: Promising drug slows brain shrinkage in progressive MS patients

A promising drug slowed brain shrinkage in progressive multiple sclerosis (MS) by nearly half, according to new research led by Cleveland Clinic. Very limited therapies are currently available for this disabling form of the disease.

The definitive results of the phase 2 trial – published in the New England Journal of Medicine– showed that the drug ibudilast decreased progression of brain atrophy in progressive MS patients by 48 percent versus placebo. The two-year SPRINT-MS study was conducted at 28 sites with 255 patients.

"These findings are significant for patients with progressive MS," said Robert Fox, M.D., the study's principal investigator and vice-chair for research in Cleveland Clinic's Neurological Institute. "Our hope is that the benefit of ibudilast in slowing brain shrinkage will also translate to decreased progression of associated physical disabilities in a future phase 3 trial."

Progressive MS is associated with gradual worsening of symptoms and increasing disability. It commonly follows relapsing-remitting MS, for which there are more than a dozen approved treatments. However, none of these therapies has consistently demonstrated efficacy in slowing disability progression in patients with progressive MS, particularly those without evidence for active inflammation.

Ibudilast, an oral drug with activity on several biologic pathways with potential relevance to progressive MS, was approved in Japan in 1989 for use in asthma and stroke. It is also being studied in the U.S. for potential treatment of amyotrophic lateral sclerosis (ALS) and drug addiction.

Additionally, the SPRINT-MS study demonstrated the utility of advanced imaging in clinical trials to measure the impact of therapies on brain health. The potential application of imaging-based outcome measures may extend beyond progressive MS to other neurodegenerative disorders as well.

"There is a significant need for new treatment options to effectively delay disability progression for patients with progressive MS," said Dr. Fox. "We are hopeful these findings will help us develop more therapies for progressive MS, and do so more rapidly and efficiently."

The research, which paves the way for phase 3 testing, also determined that ibudilast is relatively safe and well tolerated. The drug has received fast-track designation from the U.S. Food & Drug Administration.

"Although a larger study is needed to confirm these findings, this promising study brings people with progressive MS, who currently do not have many treatment options, one step closer to a potential therapy," said Robin Conwit, M.D., program director at the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.

The study was conducted by the Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT), which is sponsored by NINDS. The research was supported by NINDS, National Multiple Sclerosis Society and MediciNova.

"These results are a promising step toward a potential new therapy for people living with progressive forms of MS, for whom there are few treatment options," said Bruce Bebo, Ph.D., Executive Vice President, Research, National MS Society. "It is gratifying to see our investments in progressive MS starting to pay off."

Ref : https://en.wikipedia.org/wiki/Ibudilast

Drug used for chest pain does not decrease chance of first occurrence of ventricular arrhythmias

A clinical trial of more than 1,000 patients with implantable cardioverter defibrillators (ICDs) found that the drug ranolazine (commonly used to treat chest pain; brand name Ranexa®) was safe but didn't significantly decrease the likelihood of the first occurrence of ventricular tachycardia, ventricular fibrillation or death in this high-risk population. The study was published recently in JACC, the Journal of the American College of Cardiology.

Researchers at the University of Rochester Medical Center launched the National Institutes of Health-sponsored trial in 2011 after previous studies suggested ranolazine might cut the incidence of arrhythmias. A limited number of anti-arrhythmic therapies have been developed and tested over the past 25 years, leaving doctors and patients with older treatment options that often come with substantial side effects.

The trial, which was conducted at 95 centers in the United States and Canada, did reveal a bright spot for ranolazine: the drug lowered the number of recurring episodes of ventricular tachycardia, a fast, abnormal heart rate that begins in the ventricles (lower chambers of the heart) and can cause dizziness, lightheadedness, palpitations or loss of consciousness. The results suggest that there could be a potential role for ranolazine in patients with ICDs who can't tolerate other drugs or aren't eligible for ablation, a procedure that attempts to correct faulty heart rhythms.

"This drug is already on the market to treat chest pain, and while it didn't provide the revolutionary results we had hoped for, I think there's a place for it in the toolbox of treatments for select patients," said Wojciech Zareba, M.D., Ph.D., lead study author and professor of Cardiology at the University of Rochester Medical Center. "Ventricular tachycardia is the most common arrhythmia that individuals with ICDs experience. This drug could be an option for patients who haven't had success with other therapies."

The double-blind, placebo-controlled randomized trial included 1,012 individuals with cardiomyopathy, a disease of the heart muscle that makes it difficult for the heart to pump blood throughout the body. All participants had ICDs and were at high risk for ventricular tachycardia (VT) and ventricular fibrillation (VF), irregular heart rhythms that are associated with increased hospitalizations and death.

The average age of participants was 64 years and 18 percent were women. Half received 1,000 mg of ranolazine orally twice daily and half received a placebo pill. Approximately 34 percent of patients who took ranolazine experienced ventricular tachycardia, ventricular fibrillation or death, compared to 39 percent of individuals in the placebo group. Though the number in the ranolazine group was lower, the difference between groups was not large enough to be considered "significant" or meaningful.

Upon further analysis, the researchers found that the risk for recurrent ventricular tachycardia was 30 percent lower in patients randomized to receive ranolazine compared with placebo.

Mehmet Aktas, M.D., associate professor of Cardiology and a member of the UR Medicine Heart & Vascular team enrolled 20 patients at the University of Rochester Medical Center.

"Through this trial we learned that ranalozine can be administered safely in patients with life threatening abnormal heart rhythms and that it can be given concomitantly with other commonly used antiarrhythmic drugs," said Aktas. "This trial provides clinicians with one more treatment option for patients who have recurrent lethal arrhythmias, which is huge given that this is a very sick population for which we often have limited therapies."

A major limitation of the study was that nearly half of the study participants discontinued the study drugs (both ranolazine and placebo).

The trial, dubbed RAID (Ranolazine in High-Risk Implantable Cardioverter-Defibrillator Patients), was funded with a $9.5 million grant from the National Heart, Lung and Blood Institute at the National Institutes of Health. Gilead Sciences, Inc., the biopharmaceutical company that markets ranolazine, donated the drug and placebo needed for the trial.

Ref : http://www.onlinejacc.org/content/72/6/646
https://en.wikipedia.org/wiki/Ranolazine

Drug used to treat amoebic dysentery may block journey of rabies virus in nerves

In continuation of my update on Emetine

To successfully infect its host, the rabies virus must move from the nerve ending to the nerve cell body where it can replicate.

In a study published July 20 in the journal PLoS Pathogens, researchers from Princeton University reveal that the rabies virus moves differently compared to other neuron-invading viruses and that its journey can be blocked by a drug commonly used to treat amoebic dysentery.

Most viruses only infect the nervous system accidentally when the immune system is compromised. But some "neurotropic" viruses have evolved to target neurons as part of their normal infectious cycle. The rabies virus, for example, is transmitted when an infected animal bites into a host's muscle. It then spreads into the end terminals of motor neurons innervating the muscle and travels along the neurons' long axon fibers to the neuronal cell bodies. From there, the virus can spread throughout the central nervous system and into the salivary glands, where it can be readily transmitted to other hosts. Though rabies infections in humans are rare in the United States, the virus kills more than 59,000 people annually, according to the Centers for Disease Control and Prevention.

Alpha herpesviruses, such as herpes simplex viruses, also enter peripheral nerve terminals and move along axons to the neuronal cell body, where they can lie dormant for the life of the host.

"Transport to the neuronal cell body is not a passive process, but an active one relying on the neuron's own motor proteins and microtubule tracks," said Lynn Enquist, Princeton's Henry L. Hillman Professor in Molecular Biology, a professor of molecular biology and the Princeton Neuroscience Institute, and the study's senior author. "Virus particles must engage this machinery for efficient transport in axons, otherwise infection cannot start."

Enquist and colleagues previously found that alpha herpesviruses engage the neuronal transport machinery by stimulating protein synthesis at infected nerve terminals. Viral transport to the cell body can therefore be blocked by drugs that inhibit protein synthesis, as well as by cellular antiviral proteins called interferons.

In the current study, Enquist and colleagues investigated how the rabies virus engages the neuronal transport machinery. The researchers infected neurons with a virulent strain of the virus tagged with a red fluorescent protein, allowing the researchers to observe viral transport in real time by live-cell fluorescence microscopy.

The study was led by Margaret MacGibeny, who earned her Ph.D. in 2018, and associate research scholar Orkide Koyuncu, at Princeton, with contributions from research associate Christoph Wirblich and Matthias Schnell, professor and chair of microbiology and immunology at Thomas Jefferson University.

In contrast to alpha herpesvirus infections, the team found that interferons had no effect on rabies virus transport, perhaps because, until it reaches the neuronal cell body, the rabies virus hides out inside cellular structures called endosomes.

"We also couldn't detect increased protein synthesis in axons upon rabies virus infection," MacGibeny said. "But, to our surprise, we saw that a protein synthesis inhibitor called emetine efficiently blocked rabies virus transport to the cell body."

Emetine had no effect on the transport of endosomes devoid of the rabies virus. But endosomes carrying the virus were either completely immobilized, or were only able to move short distances at slower-than-normal speeds.

Other protein synthesis inhibitors did not block rabies virus transport, however, suggesting that emetine works by inhibiting a different process in infected neurons.

"Emetine has been used to treat amoebic dysentery," Koyuncu said. "In the laboratory it is widely used to inhibit protein synthesis but there are recent reports indicating that emetine has anti-viral effects that are independent of protein synthesis inhibition. Our study shows that this drug can inhibit rabies virus invasion of the nervous system through a novel mechanism that hasn't been reported before."

"The manuscript by MacGibeny et al. both advances and complicates our understanding of how neurotropic viruses make their way from the axon terminus to the cell body," said Professor Glenn Rall, an expert in neurotropic virus infections at Fox Chase Cancer Center, who was not involved in the study. "Revealing variations in the axonal transport of neurotropic viruses, coupled with intriguing insights into new roles for well-known drugs, has both mechanistic and clinical implications for these life-threatening infections.

"Our next step is to figure out how emetine disrupts rabies virus transport in axons," Enquist says. "Does it inhibit cell signaling pathways after rabies virus entry, or does it directly block the recruitment of motor proteins to virus-carrying endosomes?"

Ref : https://molbio.princeton.edu/news/enquist-lab-researchers-uncover-new-details-rabies-virus-movement

Chemists synthesize garlic ingredient from readily available components

Fresh garlic extracts contain a variety of healthy organosulfur compounds, among which ajoene forms a major oil-extractable ingredient. Now, chemists in the United Kingdom have synthesized ajoene from readily available components for the first time. The results, which are published in the journal Angewandte Chemie, show that ajoene is accessible on a large scale with very few synthetic steps. Chemical synthesis of biologically active compounds is important for their further evaluation in medicinal research.

If garlic is cut or chewed, enzymes present in the damaged tissue start to degrade its main organosulfur metabolite, alliin. The first degradation product is allicin, which gives fresh garlic preparations their characteristic pungent odor. However, this molecule decomposes further into various, largely oil-soluble compounds, all characterized chemically as organosulfides or disulfides. A more stable decomposition product and main component in oil extracts is ajoene. This compound has similar health-promoting effects to allicin and it exhibits anticancer activity.

Although ajoene can be isolated from garlic extracts, chemical synthesis would have many advantages. Synthesized ajoene would allow the introduction of chemical modifications, a key provision in drug research. Therefore, Thomas Wirth and his group at Cardiff University in collaboration with the Welsh company Neem Biotech in the United Kingdom have now developed a fully synthetic approach based on simple, readily available components. The sequence starts with a simple dibromide and terminates with the oxidation of an organoselenium compound. Oxidative elimination of the selenium compound, the scientists noted, leads to the formation of the terminal carbon-carbon double bond characteristic for the ajoene molecule. At the same time, its sulfide moiety is oxidized to a sulfoxide, another characteristic chemical function in ajoene.

The biggest challenge in ajoene synthesis was minimizing the various side reactions typical for organosulfur compounds, Wirth and his team reported. Such side reactions profoundly decreased the yield in the biomimetic approach to ajoene, which started from allicin. But low yields turned out to be a problem in total synthesis as well. Therefore, the scientists explored several modifications in the reaction steps, but the most profound improvement, unexpectedly, came from scaling up the synthesis. On the 200-gram scale, the final oxidation yielded 56 percent of the product, the authors reported, which was twice as much as when working on the milligram scale.

The product was biologically active. Testing its activity against bacteria in a bioassay, Wirth and his group found that synthetic ajoene performed similarly to or even better than natural ajoene extracted from garlic. It inhibited biological communication called quorum sensing in Gram-negative bacteria, which may lead to biofilm formation. Inhibiting this could be a promising usage of ajoene, the authors suggested. And as total synthesis has now made this compound more easily accessible, its career in medicinal chemistry may be ready to take off.

Ref : https://newsroom.wiley.com/press-release/angewandte-chemie-international-edition/garlic-ingredient-lab-bench-short-total-synthe

Very high levels of good cholesterol may increase risk of heart attack and death

In continuation of my update on Cholesterol

Very high levels of high-density lipoprotein (HDL or "good") cholesterol may be associated with an increased risk of heart attack and death, according to research presented today at ESC Congress 2018.

Study author Dr Marc Allard-Ratick, of Emory University School of Medicine, Atlanta, US, said: "It may be time to change the way we view HDL cholesterol. Traditionally, physicians have told their patients that the higher your 'good' cholesterol, the better. However, the results from this study and others suggest that this may no longer be the case."

HDL cholesterol has been considered "good" because the HDL molecule is involved in the transport of cholesterol from the blood and blood vessel walls to the liver and ultimately out of the body, thereby reducing the risk of clogged arteries and atherosclerosis. People with low HDL cholesterol have a greater risk of atherosclerosis and cardiovascular disease. But the protective effect of very high HDL cholesterol has been unclear.

This study, conducted as part of the Emory Cardiovascular Biobank, investigated the relationship between HDL cholesterol levels and the risk of heart attack and death in 5,965 individuals, most of whom had heart disease. The average age of participants was 63 years and 35% were female.

Participants were divided into five groups according to their HDL cholesterol level: less than 30 mg/dl (0.78 mmol/L), 31-40 mg/dl (0.8-1 mmol/L); 41-50 mg/dl (1.1-1.3 mmol/L); 51-60 mg/dl (1.3-1.5 mmol/L); and greater than 60 mg/dl (1.5 mmol/L).

During a median follow-up of four years, 769 (13%) participants had a heart attack or died from a cardiovascular cause. Participants with HDL cholesterol 41-60 mg/dl (1.1-1.5 mmol/L) had the lowest risk of heart attack or cardiovascular death. Risk was increased both in participants with low levels (less than 41 mg/dl) and very high levels (greater than 60 mg/dl) of HDL cholesterol, which produced a U-shaped curve when plotted graphically.

Participants with HDL cholesterol levels greater than 60 mg/dl (1.5 mmol/L) had a nearly 50% increased risk of dying from a cardiovascular cause or having a heart attack compared to those with HDL cholesterol levels 41-60 mg/dl (1.1-1.5 mmol/L).

The associations were consistent even after controlling for other risk factors for heart disease such as diabetes, smoking, and low-density lipoprotein (LDL or "bad") cholesterol, as well as other factors linked with high HDL cholesterol such as alcohol intake, race, and sex.

The results support findings from several large population-based studies, including a recent publication which found increased cardiovascular and all-cause death when HDL cholesterol reached extremely high levels. Dr Allard-Ratick said: "Our results are important because they contribute to a steadily growing body of evidence that very high HDL cholesterol levels may not be protective, and because unlike much of the other data available at this time, this study was conducted primarily in patients with established heart disease."

He noted that more research is needed to elucidate the mechanisms of this paradoxical association. "While the answer remains unknown, one possible explanation is that extremely elevated HDL cholesterol may represent 'dysfunctional HDL' which may promote rather than protect against cardiovascular disease," he said.

Dr Allard-Ratick concluded: "One thing is certain: the mantra of HDL cholesterol as the 'good' cholesterol may no longer be the case for everyone."

Ref : https://www.escardio.org/The-ESC/Press-Office/Press-releases/Too-much-of-a-good-thing-Very-high-levels-of-good-cholesterol-may-be-harmful

Entresto drug can be initiated early and safely in heart failure patients with reduced ejection fraction

In continuation of my update on sacubitril/valsartan

Data from the TRANSITION study presented today at the European Society of Cardiology (ESC) Congress in Munich, Germany has shown that Entresto® (sacubitril/valsartan) can be initiated early and safely in a wide range of heart failure patients with reduced ejection fraction (HFrEF) who have been stabilized after hospitalization due to an acute heart failure episode. Patients involved in the study included those with no prior experience of Entresto or conventional HF therapies, as well as those with prior experience of conventional HF therapies.

About half of all heart failure patients have reduced ejection fraction, and optimizing treatment for these patients according to guidelines is critical to reduce the likelihood of another acute episode or dying. However, there is often hesitancy to initiate a new treatment after a hospitalization as these patients are considered 'vulnerable' and unable to tolerate changes in their medication.

"In the weeks following an episode of acute heart failure, patients are very vulnerable and face a high risk of re-hospitalization and death," said Prof. Rolf Wachter, University Hospital Leipzig, Germany and study investigator. "The PARADIGM-HF study showed that sacubitril/valsartan reduces heart failure-related hospitalizations, re-hospitalization and death. TRANSITION shows that sacubitril/valsartan can be initiated early and safely in patients shortly after an acute heart failure episode, providing physicians with added confidence to optimize their care with innovative medicines in heart failure treatment."

In TRANSITION, the safety and tolerability of Entresto were assessed in HFrEF patients after they have been stabilized following an acute heart failure episode. Patients were randomized to initiate Entresto therapy either in the hospital (pre-discharge) or shortly after leaving the hospital (post-discharge). At 10 weeks, more than 86% of patients were receiving Entresto for 2 weeks or longer without interruption and about half of patients in the study achieved the primary endpoint which was a target dose of 200 mg of Entresto twice daily within 10 weeks in both groups. The number of patients who met the primary and secondary endpoints was similar across both treatment arms. The incidence of adverse events and discontinuations of Entresto due to adverse events was also similar in both the in-hospital and the out-patient setting.

"We are encouraged by the findings of TRANSITION which show that Entresto, the new standard of care in heart failure, can be safely initiated in recently hospitalized patients," said Shreeram Aradhye, MD, Chief Medical Officer and Global Head, Medical Affairs, Novartis Pharmaceuticals. "Heart failure is a serious progressive disease with 83% of patients hospitalized at least once for an acute heart failure episode during the course of their condition. Hospitalization provides an opportunity for physicians to optimize heart failure treatment according to guidelines to reduce the likelihood of hospital readmission and death, reduce the burden of hospitalizations, and improve patient outcomes."

Ref : https://www.novartis.com/news/media-releases/novartis-announces-new-data-show-entresto-sacubitrilvalsartan-can-be-initiated-early-safely-hospitalized-patients-after-acute-heart-failure-episode

Food scientists turn soy milk residue into healthy probiotic drink

In continuation of my update on Soy Milk

Food scientists at the National University of Singapore (NUS) have given okara - the residue from the production of soy milk and tofu, and is usually discarded - a new lease of life by turning it into a refreshing drink that contains live probiotics, dietary fiber, free isoflavones and amino acids. By encapsulating these nutrients in a beverage, they can be easily absorbed into the body, and promote gut health.

Created using a patented, zero-waste process, the tasty drink can be stored at room temperature for up to six weeks and still retain high counts of live probiotics to better deliver health effects. This is unlike commercially available probiotic drinks which are mainly dairy-based and require refrigeration to maintain their levels of live probiotics. These beverages also have an average shelf-life of four weeks, and do not contain free isoflavones, which have a host of health benefits.

"Okara has an unpleasant smell and taste - it smells fishy, tastes bland, and has a gritty mouthfeel. Our breakthrough lies in our unique combination of enzymes, probiotics and yeast that work together to make okara less gritty, and give it a fruity aroma while keeping the probiotics alive. Our final product offers a nutritious, non-dairy alternative that is eco-friendly," said project supervisor Associate Professor Shao-Quan Liu, who is from the Food Science and Technology Program at the NUS Faculty of Science.

Turning unwanted soy pulp into a nutritious drink

About 10,000 tonnes of okara are produced yearly in Singapore. As it turns bad easily, causing it to give out an unpleasant smell and a sour taste, okara is usually discarded by soy food producers as food waste.

The idea of using fermentation to produce a drink from okara was first conceived by Ms Weng-Chan Vong, a PhD student from the NUS Food Science and Technology Program. She recounted, "Fermented soy products, such as soybean paste and miso, are common in Asian food culture. When I was young, my grandparents explained to me how these fermented foods are made. The fermentation process was like magic to me - it transforms bland food into something delicious."

"During my undergraduate studies at NUS, I worked on a project to examine how soy milk can be infused into different food items, and I realized that a huge amount of okara was being discarded. It occurred to me that fermentation can be one good way to convert unwanted okara into something that is nutritious and tastes good," she added.

Under the guidance of Assoc Prof Liu, Ms Vong took a year to devise a novel recipe that converts okara into a beverage that is fruity and refreshing. She experimented with 10 different yeasts and four different enzymes before coming up with an ideal combination.

The final recipe uses the probiotic strain Lactobacillus paracasei L26, the Viscozyme ® L enzyme and the Lindnera saturnus NCYC 22 yeast to convert the okara into a nutritious drink that achieves a minimum of 1 billion probiotics per serving, which is the current recommendation by the International Scientific Association for Probiotics and Prebiotics to achieve maximum health benefits. The drink, which takes about one and a half days to produce, also contains free isoflavones, which are naturally occurring antioxidants that maintain cardiovascular health, as well as dietary fiber and amino acids.

Next step: Refining the recipe for commercialization

The NUS researchers have filed a patent for their novel technique, and are currently experimenting with different enzymes and microorganisms to refine their recipe. They are also looking to collaborate with industry partners to introduce the drink to consumers.

"In recent years, the food and beverage industry has been intensifying efforts to develop products that appeal to consumers who are increasingly health conscious. Our new product offers soy food manufacturers a viable solution to reduce waste, and also enables them to provide a healthy and eco-friendly beverage for their customers," said Assoc Prof Liu.

Matcha green tea kills breast cancer stem cells

MATCHA, the Green Tea packed with antioxidants, is often hailed as containing properties which prevent disease.

Scientists in Salford, UK have shed a ray of light on the claim by testing it on cancer stem cells - with surprising results.

In research published in the journal Aging, a team from the Biomedical Research Centre at the University of Salford, used metabolic phenotyping on cell lines of breast cancer stem cells and found that Matcha "shifted cancer cells towards a quiescent metabolic state" and stopped their spread at a relatively low concentration (0.2 mg/ml).

They also found that the signaling pathways that promote cancer stem cells indicated that Matcha "strongly affected mTOR signals, weakening components of the 40S ribosome. This raised the possibility that Matcha could be used in place of chemical drugs such as rapamycin.

Michael Lisanti, professor of translational medicine at the center, explained: "Matcha green tea is a natural product used as a dietary supplement with great potential for a range of treatments. But, the molecular mechanism underpinning all that remains largely unknown.

"By using metabolic phenotyping, we found that the tea is suppressing oxidative mitochondrial metabolism - in other words it is preventing the cells from 're-fuelling' and therefore they become inactive and die.

"The effects on human breast cancer cells were very striking; the active ingredients in matcha having a surgical effect in knocking out certain signaling pathways.

"Our results are consistent with the idea that Matcha may have significant therapeutic potential, mediating the metabolic reprogramming of cancer cells."

The team who specialize in identifying non-toxic methods of killing cancer stem cells recently found that Earl Grey tea ingredient, Bergamot kills cancer cells and works as an anti-cholesterol agent.

Ref : https://www.salford.ac.uk/news/articles/2018/green-tea-prevent-cancer-cells-from-refuelling