Health Research Report

157th Issue Date 15JUN 2013

Compiled By Ralph Turchiano

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In this Issue:

1.   Nontoxic cancer therapy proves effective against metastatic cancer

2.   New research shows cheese may prevent cavities

3.   Vitamin D deficiency may help spread of hepatitis B throughout liver

4.   Formula-feeding linked to metabolic stress and increased risk of later disease

5.   Vitamin C may be beneficial against exercise-induced bronchoconstriction

6.   Cocoa may help fight obesity-related inflammation

7.   Do antidepressants impair the ability to extinguish fear?

Nontoxic cancer therapy proves effective against metastatic cancer

The mouse model study by University of South Florida researchers combined ketogenic diet and hyperbaric oxygen therapy

Tampa, FL (June 5, 2013) — A combination of nontoxic dietary and hyperbaric oxygen therapies effectively increased survival time in a mouse model of aggressive metastatic cancer, a research team from the Hyperbaric Biomedical Research Laboratory at the University of South Florida has found.

The study, “The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic Cancer,” was published online today in PLOS ONE.

Led by Dominic D’Agostino, PhD, principal investigator in the Department of Molecular Pharmacology and Physiology at the USF Health Morsani College of Medicine, the research shows the effects of combining two nontoxic adjuvant cancer therapies, the ketogenic diet and hyperbaric oxygen therapy, in a mouse model of late-stage, metastatic cancer.

“Our study demonstrates the potential of these cost-effective, nontoxic therapies to contribute to current cancer treatment regimens and significantly improve the outcome of patients with advanced metastatic cancer,” D’Agostino said.

Metastasis, the spreading of cancer from the primary tumor to distant spots, is responsible for over 90 percent of cancer-related deaths in humans. A lack of available therapies effective against metastatic disease remains the largest obstacle in finding a cure for cancer.

In the study, mice with advanced metastatic cancer were fed either a standard high carbohydrate diet or carbohydrate-restricted ketogenic diet. Mice on both diets also received hyperbaric oxygen therapy, which uses a special chamber to increase the amount of oxygen in the tissues.

The ketogenic diet forces a physiological shift in substrate utilization from glucose to fatty acids and ketone bodies for energy. Normal healthy cells readily adapt to using ketone bodies for fuel, but cancer cells lack this metabolic flexibility, and thus become selectively vulnerable to reduced glucose availability. Solid tumors also have areas of low oxygen, which promotes tumor growth and metastatic spread.

Hyperbaric oxygen therapy involves breathing 100 percent oxygen at elevated barometric pressure, saturating the tumors with oxygen. When administered properly, both the ketogenic diet and hyperbaric oxygen therapy are non-toxic and may even protect healthy tissues while simultaneously damaging cancer cells, D’Agostino said.

While both therapies slowed disease progression independently, animals receiving the combined ketogenic diet and hyperbaric oxygen therapy lived 78 percent longer than mice fed a standard high-carbohydrate diet.

The research, funded by a charitable donation from Scivation, was inspired by the research of Professor Thomas Seyfried of Boston College. Dr. Seyfried has advanced the theory that cancer is a metabolic disease, inspiring the development of metabolic strategies to treat and prevent cancer.

D`Agostino`s team is currently collaborating with Dr. Seyfried and other scientists to secure funding and develop protocols for establishing human clinical trials.

New research shows cheese may prevent cavities

CHICAGO (June 5, 2013)—Consuming dairy products is vital to maintaining good overall health, and it’s especially important to bone health. But there has been little research about how dairy products affect oral health in particular. However, according to a new study published in the May/June 2013 issue of General Dentistry, the peer-reviewed clinical journal of the Academy of General Dentistry (AGD), consuming cheese and other dairy products may help protect teeth against cavities.

The study sampled 68 subjects ranging in age from 12 to 15, and the authors looked at the dental plaque pH in the subjects’ mouths before and after they consumed cheese, milk, or sugar-free yogurt. A pH level lower than 5.5 puts a person at risk for tooth erosion, which is a process that wears away the enamel (or protective outside layer) of teeth. “The higher the pH level is above 5.5, the lower the chance of developing cavities,” explains Vipul Yadav, MDS, lead author of the study.

The subjects were assigned into groups randomly. Researchers instructed the first group to eat cheddar cheese, the second group to drink milk, and the third group to eat sugar-free yogurt. Each group consumed their product for three minutes and then swished with water. Researchers measured the pH level of each subject’s mouth at 10, 20, and 30 minutes after consumption.

The groups who consumed milk and sugar-free yogurt experienced no changes in the pH levels in their mouths. Subjects who ate cheese, however, showed a rapid increase in pH levels at each time interval, suggesting that cheese has anti-cavity properties.

The study indicated that the rising pH levels from eating cheese may have occurred due to increased saliva production (the mouth’s natural way to maintain a baseline acidity level), which could be caused by the action of chewing. Additionally, various compounds found in cheese may adhere to tooth enamel and help further protect teeth from acid.

“It looks like dairy does the mouth good,” says AGD spokesperson Seung-Hee Rhee, DDS, FAGD. “Not only are dairy products a healthy alternative to carb- or sugar-filled snacks, they also may be considered as a preventive measure against cavities.”

Vitamin D deficiency may help spread of hepatitis B throughout liver

Researchers from Germany have found that low levels of vitamin D are associated with high levels of hepatitis B virus (HBV) replication. Findings published online in Hepatology, a journal of the American Association for the Study of Liver Diseases, suggest seasonal fluctuations in vitamin D and HBV levels point to a link in these variables among patients with chronic HBV.

While highly effective vaccines are available, HBV still remains one of the most significant infectious diseases worldwide. In fact, the World Health Organization (WHO) states that HBV is 50 to 100 times more infectious than human immunodeficiency virus (HIV). Furthermore WHO reports that two billion individuals have been infected with HBV, which is responsible for nearly 600,000 deaths each year. In the U.S. the Centers for Disease Control and Prevention (CDC) estimates that up to 1.4 million Americans are living with chronic HBV.

“Vitamin D helps maintain a healthy immune system and there is evidence of its role in inflammatory and metabolic liver disease, including infection with hepatitis C virus (HCV),” explains lead investigator Dr. Christian Lange from Johann Wolfgang Goethe University Hospital in Frankfurt. “However, the relationship between vitamin D metabolism and chronic HBV infection remains unknown and is the focus of our present study.”

Between January 2009 and December 2010, the team recruited 203 patients with chronic HBV who had not previously received treatment for their infection. Levels of 25-hydroxyvitamin D were measured from each participant. Patients co-infected with HCV, HIV, or hepatitis D; those with excessive alcohol use; and those with liver cancer or other malignancies were excluded.

Results show that 34% of participants had severe vitamin D deficiency (less than 10 ng/mL), 47% with vitamin D insufficiency (between 10-20 ng/mL) and 19% had normal levels of vitamin D (greater than 20 ng/mL). Further analyses indicate that the concentration of HBV in the blood, known as viral load, was a strong indicator of low vitamin D levels. In patients with HBV DNA less than 2000 IU/mL versus 2000 IU/mL or more, the levels of vitamin D were 17 and 11 ng/mL, respectively.

Researchers also determined that patients with the hepatitis B antigen (HBeAg) had lower levels of vitamin D than HBeAg negative participants. Inverse seasonal fluctuations between vitamin D and HBV levels were noted, which further suggests a relationship between the two variables.

“Our data confirm an association between low levels of vitamin D and high concentrations of HBV in the blood,” concludes Dr. Lange. “These findings differ from previous research of patients with chronic hepatitis C, which found no connection between vitamin D levels and concentration of HCV in the blood.” The authors propose further investigation of vitamin D as a therapeutic intervention for controlling HBV.

Formula-feeding linked to metabolic stress and increased risk of later disease

New evidence from research suggests that infants fed formula, rather than breast milk, experience metabolic stress that could play a part in the long-recognized link between formula-feeding and an increased risk of obesity, type 2 diabetes and other conditions in adult life. The study appears in ACS’ Journal of Proteome Research.

Carolyn Slupsky and colleagues explain that past research showed a link between formula-feeding and a higher risk for chronic diseases later in life. Gaps exist, however, in the scientific understanding of the basis for that link.

The scientists turned to rhesus monkeys, stand-ins for human infants in such research, that were formula-fed or breast-fed for data to fill those gaps.

Their analysis of the monkeys’ urine, blood and stool samples identified key differences between formula-fed and breast-fed individuals. It also produced hints that reducing the protein content of infant formula might be beneficial in reducing the metabolic stress in formula-fed infants. “Our findings support the contention that infant feeding practice profoundly influences metabolism in developing infants and may be the link between early feeding and the development of metabolic disease later in life,” the study states.

Vitamin C may be beneficial against exercise-induced bronchoconstriction

Vitamin C may substantially reduce bronchoconstriction caused by exercise, says Dr. Harri Hemila from the University of Helsinki, Finland. Hemila’s meta-analysis “Vitamin C may alleviate exercise-induced bronchoconstriction” was published in BMJ Open (7 June, 2013)

Exercise-induced bronchoconstriction means the transient narrowing of the airways that occurs during or after exercise. It can cause symptoms such as cough, wheezing and the shortness of breath. Formerly, this condition was called exercise-induced asthma. Usually, the diagnosis of exercise-induced bronchoconstriction is based on a 10% or greater decline in forced expiratory volume in 1 second (FEV1) caused by exercise. About 10% of the general population suffers from exercise-induced bronchoconstriction, but among some fields of competitive winter sports the prevalence can be up to 50%.

Previously, vitamin C was found to halve the incidence of common cold episodes in people enduring heavy short-term physical stress, which indicated that vitamin C might also have other effects on people under heavy physical exertion. The new systematic review focused on the effect of vitamin C on bronchoconstriction caused by exercise and identified three relevant randomized placebo-controlled trials. Each of the three identified trials found that vitamin C halved the FEV1 decline caused by exercise challenge test. The pooled estimate of vitamin C effect indicated a 48% reduction in the FEV1 decline caused by exercise.

Dr. Hemila concludes that given the low cost and safety of vitamin C and the consistency of positive findings in three randomized trials on EIB, it seems reasonable for physically active people to test vitamin C on an individual basis if they have respiratory symptoms such as cough associated with exercise

Cocoa may help fight obesity-related inflammation

A few cups of hot cocoa may not only fight off the chill of a winter’s day, but they could also help obese people better control inflammation-related diseases, such as diabetes, according to Penn State researchers.

Mice that were fed cocoa with a high-fat diet experienced less obesity-related inflammation than mice fed the same high-fat diet without the supplement, said Joshua Lambert, associate professor of food science. The mice ate the human equivalent of 10 tablespoons of cocoa powder — about four or five cups of hot cocoa — during a 10-week period.

“What surprised me was the magnitude of the effect,” Lambert said. “There wasn’t as big of an effect on the body weight as we expected, but I was surprised at the dramatic reduction of inflammation and fatty liver disease.”

The researchers reported that several indicators of inflammation and diabetes in the mice that were fed the cocoa supplement were much lower than the mice that were fed the high-fat diet without the cocoa powder and almost identical to the ones found that were fed a low-fat diet in the control group.

For example, they had about 27 percent lower plasma insulin levels than the mice that were not fed cocoa. High levels of insulin can signal that a patient has diabetes.

The cocoa powder supplement also reduced the levels of liver triglycerides in mice by a little more than 32 percent, according to Lambert, who worked with Yeyi Gu, graduate student in food science, and Shan Yu, a graduate student in physiology. Elevated triglyceride levels are a sign of fatty liver disease and are related to inflammation and diabetes.

The mice also saw a slight but significant drop in the rate of body weight gain, according to the researchers, who reported their findings in the online version of the European Journal of Nutrition.

While researchers have linked obesity-related chronic inflammation to several diseases, including type 2 diabetes and fatty liver disease, the reason for the inflammation response is not completely known. Lambert said two theories on inflammation and obesity that have emerged may help explain cocoa’s role in mitigating inflammation. In one theory, Lambert said excess fat may activate a distress signal that causes immune cells to become activated and cause inflammation. The cocoa may reduce the precursors that act as a distress signal to initiate this inflammatory response.

Lambert said that another theory is that excess fat in the diet interferes with the body’s ability to keep a bacterial component called endotoxin from entering the bloodstream through gaps between cells in the digestive system — gut barrier function — and alerting an immune response. The cocoa in this case may help improve gut barrier function.

Cocoa, although commonly consumed in chocolate, actually has low-calorie content, low-fat content and high-fiber content.

“Most obesity researchers tend to steer clear of chocolate because it is high in fat, high in sugar and is usually considered an indulgence,” Lambert said. “However, cocoa powder is low in fat and low in sugar. We looked at cocoa because it contains a lot of polyphenolic compounds, so it is analogous to things like green tea and wine, which researchers have been studying for some of their health benefits.”

Lambert said he expects future research will be conducted to better identify why the cocoa powder is effective in treating inflammation, as well as determine if the treatment is suitable for humans.

Do antidepressants impair the ability to extinguish fear?

Answers from a new study in Biological Psychiatry

An interesting new report of animal research published in Biological Psychiatry suggests that common antidepressant medications may impair a form of learning that is important clinically.

Selective serotonin reuptake inhibitors, commonly called SSRIs, are a class of antidepressant widely used to treat depression, as well as a range of anxiety disorders, but the effects of these drugs on learning and memory are poorly understood.

In a previous study, Nesha Burghardt, then a graduate student at New York University, and her colleagues demonstrated that long-term SSRI treatment impairs fear conditioning in rats. As a follow-up, they have now tested the effects of antidepressant treatment on extinction learning in rats using auditory fear conditioning, a model of fear learning that involves the amygdala. The amygdala is a region of the brain vitally important for processing memory and emotion.

They found that long-term, but not short-term, SSRI treatment impairs extinction learning, which is the ability to learn that a conditioned stimulus no longer predicts an aversive event.

“This impairment may have important consequences clinically, since extinction-based exposure therapy is often used to treat anxiety disorders and antidepressants are often administered simultaneously,” said Dr. Burghardt. “Based on our work, medication-induced impairments in extinction learning may actually disrupt the beneficial effects of exposure-therapy.”

This finding is consistent with the results of several clinical studies showing that combined treatment can impede the benefits of exposure therapy or even natural resilience to the impact of traumatic stress at long-term follow-up.

The authors also suggest a mechanism for this effect on fear learning. They reported that the antidepressants decreased the levels of one of the subunits of the NMDA receptor (NR2B) in the amygdala. The NMDA receptor is critically involved in fear-related learning, so these reductions are believed to contribute to the observed effects.

Dr. John Krystal, Editor of Biological Psychiatry, commented, “We know that antidepressants play important roles in the treatment of depression and anxiety disorders. However, it is important to understand the limitations of these medications so that we can improve the effectiveness of the treatment for these disorders.”

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These reports are done with the appreciation of all the Doctors, Scientist, and other Medical Researchers who sacrificed their time and effort. In order to give people the ability to empower themselves. Without base aspirations of fame, or fortune. Just honorable people, doing honorable things.