Health Research Report
WHITE PAPER /ROUGH COPY
167th Issue Date 01 NOV 2013
Compiled By Ralph Turchiano
In this Issue:
· Coffee consumption reduces risk of liver cancer
· How does ursolic acid induce neural regeneration after sciatic nerve injury?
· Potential Cancer and Multiple Sclerosis Treatments from Cannabinoids
· Oregon researchers say supplement cuts muscle loss in knee replacements
· Study examines expedited FDA drug approvals, safety questions remain
· HDL cholesterol controls blood glucose
· Oligomeric proanthocyanidin suppresses the death of retinal ganglion cells
Coffee consumption reduces risk of liver cancer
Bethesda, MD (Oct. 22, 2013) — Coffee consumption reduces risk of hepatocellular carcinoma (HCC), the most common type of liver cancer, by about 40 percent, according to an up-to-date meta-analysis published in Clinical Gastroenterology and Hepatology, the official clinical practice journal of the American Gastroenterological Association. Further, some data indicate that three cups of coffee per day reduce liver cancer risk by more than 50 percent.
“Our research confirms past claims that coffee is good for your health, and particularly the liver,” said Carlo La Vecchia, MD, study author from the department of epidemiology, Istituto di Ricerche Farmacologiche “Mario Negri,” and department of clinical sciences and community health, Università degli Studi di Milan, Italy. “The favorable effect of coffee on liver cancer might be mediated by coffee’s proven prevention of diabetes, a known risk factor for the disease, or for its beneficial effects on cirrhosis and liver enzymes.”
Researchers performed a meta-analysis of articles published from 1996 through September 2012, ultimately studying 16 high-quality studies and a total of 3,153 cases. This research fills an important gap as the last meta-analysis was published in 2007, and since then there has been data published on more than 900 cases of HCC.
Despite the consistency of results across studies, time periods and populations, it is difficult to establish whether the association between coffee drinking and HCC is causal, or if this relationship may be partially attributable to the fact that patients with liver and digestive diseases often voluntarily reduce their coffee intake.
“It remains unclear whether coffee drinking has an additional role in liver cancer prevention,” added Dr. La Vecchia. “But, in any case, such a role would be limited as compared to what is achievable through the current measures.”
Primary liver cancers are largely avoidable through hepatitis B virus vaccination, control of hepatitis C virus transmission and reduction of alcohol drinking. These three measures can, in principle, avoid more than 90 percent of primary liver cancer worldwide.
Liver cancer is the sixth most common cancer in the world, and the third most common cause of cancer death. HCC is the main type of liver cancer, accounting for more than 90 percent of cases worldwide. Chronic infections with hepatitis B and C viruses are the main causes of liver cancer; other relevant risk factors include alcohol, tobacco, obesity and diabetes.
How does ursolic acid induce neural regeneration after sciatic nerve injury?
Ursolic acid (chemical name 3-hydroxy-12- ursen-28-oic acid) is a triterpenoid extracted from natural plant-based drugs, and has anti-oxidative, anti-inflammatory, anti-apoptotic, and anti-scarring effects, and it regulates the immune system and promotes the repair of injured neurons.However, no reports have explored its role in peripheral nerve injury. A recent study by Prof. Jiajun Chen and team from China-Japan Union Hospital of Jilin University, China established mouse models of sciatic nerve injury through unilateral sciatic nerve complete transection and microscopic anastomosis. The successfully generated model mice were treated with 10, 5, or 2.5 mg/kg ursolic acid via intraperitoneal injection. This study, published in the Neural Regeneration Research (Vol. 8, No. 27, 2013), is the first to demonstrate a role of ursolic acid in repair and regeneration following peripheral nerve injury. Ursolic acid promoted the regeneration of injured nerve myelin sheaths and reconstructed muscular functions. All experimental findings provide favorable evidence for the application of ursolic acid following peripheral nerve injury.
Potential Cancer and Multiple Sclerosis Treatments from Cannabinoids
Contributing Author Claire Duplan
The search for potential medical applications for the compounds that are present in the marijuana or cannabis plant has included studies into the efficacy of various compounds for the treatment of a range of diseases, including cancer, multiple sclerosis, anxiety and depression. However, although advances have been made in strategies to limit the addictive effects of drugs like cannabis, the use of these compounds in medicine has been hampered by the potential for adverse effects.
Medical Research into Cannabis-Derived Compounds
Much of the research has involved isolating compounds found in the cannabis plant and testing their efficacy as medical treatments. Researchers isolated the primary active component of cannabis, tetrahydrocannabinol (THC) in 1964, but any potential medical applications of this compound must take into account its negative side effects, including its hallucinogenic and addictive properties. Addiction is a significant consideration for pharmaceutical drugs as well as illegal substances, since it can lead to serious additional health and social problems, as described by DrugAbuse.com. Researchers have therefore attempted to find non-addictive substances in the cannabis plant that might have similar medicinal effects, leading to the discovery of a cannabinoid that may help to treat multiple sclerosis (MS) just as effectively as THC, as well as to the recent research into the anti-cancer properties of cannabinoids.
Cannabinoids for Multiple Sclerosis Treatment
A study of cannabidiol (CBD), which is the second most plentiful cannabinoid in the marijuana plant, after THC, found that it could effectively reduce the type of inflammation associated with MS, without risking the same mind-altering side effects. The researchers treated mouse immune cells of the type that can attack and damage the brain and spinal cord, with either THC or CBD, and found that both chemicals reduced production of inflammatory molecules. The effect was particularly strong for the production of interleukin 17, a molecule that has been associated with the nerve cell damage that occurs in MS, a disease in which the immune system attacks the nervous system. Both THC and CBD appeared to prevent the immune cells from producing the inflammatory molecules that can harm the nerve cells, suggesting that they might be useful for the treatment of MS. The therapeutic potential of CBD is particularly exciting, since it does not carry the same risk of side effects as THC.
Cannabinoids for Cancer Treatment
A similarly important result was obtained in a study that looked at the potential for non-THC compounds from the marijuana plant to act against cancer cells. THC had previously been found to have significant anti-cancer properties, but as in the case of MS, the addictive and mind-altering qualities of the chemical had offset these benefits and raised concerns about its use in medicine. The new study examined the efficacy of a selection of other cannabis-derived compounds as anti-cancer agents.
The study was conducted by a group based at St George’s, University of London, which has previously undertaken research into the potential medical uses of cannabis-derived compounds. The current work explored the anti-cancer activity of six cannabinoid compounds. Two of these were different forms of cannabidiol, two were cannabigevarins, and two were cannabigerols. Together, these six compounds represent the most abundant forms of cannabinoids in the marijuana plant, other than the hallucinogenic THC. All of these cannabinoids lack the mind altering properties of THC, making them potentially more useful chemicals for medical treatment.
The researchers, led by Dr Wai Liu, tested the anti-cancer activity of these compounds against leukemia cells. Each of the six cannabinoids that was studied was found to be just as effective against cancer cells as THC, and when used in combination with one another, they were found to produce even greater effects. The cannabinoids were able to prevent the growth and development of the cancer cells, and even to kill them when applied in specific dosages.
Dr Liu believes that these cannabinoids show great promise as anti-cancer drugs, and are likely to produce minimal side effects, especially when compared to a compound like THC, which is known to have potential negative effects in addition to its anti-cancer properties. Cannabinoids can be produced easily and inexpensively, making them a potential source of new, lower cost cancer treatments. He describes this study as “a critical step in unpicking the mysteries of cannabis as a source of medicine”, a mystery that his research group will continue to explore in the future, particularly by testing the use of cannabinoids in combination with existing cancer treatments.
Oregon researchers say supplement cuts muscle loss in knee replacements
Package of 8 essential amino acids, taken after physical therapy, also helps to speed recovery
EUGENE, Ore. — (Oct. 25, 2013) — Twenty grams of essential amino acids taken twice daily for a week before and for two weeks after knee-replacement surgeries helped 16 patients, mean age 69, recover faster and with much less muscle atrophy than a control group ingesting a placebo.
The approach — detailed in a paper now online ahead of print in the Nov. 13 issue of the Journal of Clinical Investigation — could spell relief and speed recovery for a growing population of aging adults who face total knee-replacements because of loss of mobility and pain problems. An estimated 3.48 million Americans are projected to need the surgery, known as total knee arthroplasty (TKA), by 2030.
The findings are part of an ongoing collaboration led by Hans C. Dreyer, a professor of human physiology at the University of Oregon, with the Eugene-based Slocum Research & Education Foundation and the Oregon Research Institute.
Atrophy in the quadriceps, a group of four muscles on the front of the thigh, has been a long-running problem following knee-replacement surgeries, Dreyer said.
In the study, 12 members of a control group receiving 40 grams a day of a non-essential amino acid supplement, a placebo, averaged an 18.4 loss in quadriceps muscle mass in their operated leg six weeks after surgery; those getting the supplement of eight essential amino acids (EEA) averaged a 6.2 percent loss. Eighty percent of atrophy occurred in the first two weeks after surgery. Atrophy in non-operative legs was about 50 percent of that in the operative leg in both groups. Muscle mass changes were seen with magnetic resonance imaging done at two and six weeks after surgery.
“We’ve learned that the essential amino acids were able to mitigate the amount of muscle loss,” Dreyer said. “The functional measures that we looked at — getting up out of a chair, going up a flight of stairs and going back down the stairs — were all back to baseline in the treatment group, whereas in the placebo group those times on all of the functional measures were much longer. That suggests that this is a means at which we can accelerate functional recovery.”
Faster recovery is a big plus for patients, because most of them have been dealing with pain for a long time, said Dr. Brian A. Jewett, a surgeon at the Slocum Center for Orthopedics & Sports Medicine.
“Walking and being physically active are difficult for them pre-operatively and post-operatively, but for different reasons,” he said. “Surgery removes the pre-operative pain and disability, and physical therapy helps restore range of motion and strength post-operatively. EAA appear to facilitate this process, presumably by reducing muscle loss. In the end, if I can get my patients able to go up and down stairs and get up from a chair sooner then this is much better for their overall health, and we saw this occur 6 weeks after surgery in the EAA group. This also suggests a durability-of-treatment effect because EAA treatment was stopped two weeks after surgery and functional mobility measures were recorded four weeks later, or six weeks after TKA. This is clinically very important to me and my patients.”
Six weeks after surgery, patients in the control group took 32 percent more time to rise from a chair, walk three meters (about 10 feet), turn around and sit back down, compared to before surgery. Patients receiving essential amino acids took about the same amount of time as before surgery. Control patients took even longer to maneuver stairs after surgery. Again, times remained the same for the EEA group pre- and post-operatively.
“As we’ve measured it,” Dreyer said, “many who have this surgery experience significant and rapid loss of muscle mass despite the fact that their activity level does not change dramatically relative to pre-surgery, which is low to begin with because of their knee pain.”
The essential amino acid supplement contained rapidly absorbed raw amino acids — a mix of histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine and valine. Essential amino acids, which are not naturally produced by the body and must come from food sources, help the body in many ways, including tissue repair.
The placebo was alanine, a non-essential amino acid. Both supplements were mixed into pudding, cereal or carbonated beverage based on patient choice. Supplements were consumed an hour after physical therapy to take advantage of optimum protein synthesis after resistance exercises.
Researchers hope to expand their work to see how a longer duration of supplementation affects patients at six months and a year after surgery. Another potential benefit, Jewett said, is that combined with technological improvements in the components used in knee-joint replacement surgeries, such supplementation with essential amino acids may allow for the possibility of patients who elect to undergo surgery earlier in life to return to work and daily activities faster, which are important outcomes for patients.
“If this supplementation can accelerate recovery and reduce muscle loss, then that represents an advancement in TKA that has not received as much attention as component development and survivorship,” Jewett said. “In other words, essential amino acids supplementation represents a major advancement on the rehabilitation front. I think about EAA supplementation as a potentially low-cost opportunity to jump-start the rehab process. We know that patients who are more engaged participants in their post-operative therapy often have better outcomes. Our ability to mitigate muscle atrophy may lead to earlier achievement of functional mobility, which gets our patients out of the hospital, back in their homes, to work and enjoying recreational activities faster, and that’s my goal as their surgeon.”
Dreyer’s group is pursuing a grant for a five-year, single-site clinical trial to follow patients for up to a year to explore longer-term impacts of EAA supplementation on muscle volume and functional mobility. Also included are studies designed to identify the mechanisms of action, the durability of effect and the safety and potential benefits of longer dosing times. The group also plans to assess the impacts of treatment on the quality of life of patients and their engagement, or patient activation, in their own health-care needs.
“Researchers at the University of Oregon and their collaborators are making important discoveries that promise to improve people’s lives and benefit human health,” said Kimberly Andrews Espy, vice president for research and innovation and dean of the graduate school at the University of Oregon. “This study may result in better outcomes for the millions of people who undergo knee replacement surgeries and represents the tremendous value of these kinds of innovative research-industry partnerships.”
Study examines expedited FDA drug approvals, safety questions remain
Fewer patients were studied as part of expedited reviews of new drugs approved by the U.S. Food and Drug Administration (FDA) in 2008 and some safety questions remain unanswered, according to a study published by JAMA Internal Medicine, a JAMA Network publication.
The FDA is authorized to make new drugs available more quickly if they would be a significant therapeutic advancement and if they fulfill unmet therapeutic needs for serious illnesses, according to the study background.
Thomas J. Moore, A.B., of the Institute for Safe Medication Practices, Alexandria, Va., and Curt D. Furberg, M.D., Ph.D., of the Wake Forest School of Medicine, Winston-Salem, N.C., examined development times, clinical testing, post-market follow-up and safety risks for the new drugs approved by the FDA in 2008, when most provisions of current law, regulation and policies were in effect.
That year, the FDA approved 20 therapeutic drugs (eight under expedited review and 12 under standard review). The study findings indicate that expedited drugs took a median (midpoint) of 5.1 years of clinical development to get marketing approval compared with 7.5 years for the drugs that underwent standard review, according to the study results.
The expedited drugs were tested for efficacy in a median 104 patients compared with a median 580 patients for standard review. By 2013, many postmarketing studies to gather additional evidence on the safety of expedited drugs had not been completed, according to researchers.
“The testing of new drugs has shifted from a situation in which most testing was conducted prior to initial approval to a situation in which many innovative drugs are more rapidly approved after a small trial in a narrower patient population with extensive additional testing conducted after approval,” the authors conclude. “Our findings suggest that the shift has made it more difficult to balance the benefits and risks of new drugs. Further systematic assessment of the standards and procedures for testing new drugs is needed.”
(JAMA Intern Med. Published online October 28, 2013. doi:10.1001/jamainternmed.2013.11813. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Commentary: Can Expedited Drug Approval Without Expedited Follow-up Be Trusted?
In a related commentary, Daniel Carpenter, Ph.D., of Harvard University, Boston, writes: “The findings of Moore and Furberg underscore the continuing importance of rigorous premarket studies of ample size. If the critical phrase ‘serious or life-threatening conditions that would address an unmet medical need’ is defined broadly enough (and there are lobbying efforts to define it as broadly as possible), the future of evidence for pharmaceuticals in the United States will look more like 100 patients for efficacy trials instead of 500 patients.”
“If the FDA’s requirements for new drugs, both premarket and postmarket, are weakened, trust in both the efficacy and safety of prescription drugs is likely to be weakened. The stakes of the current policy debates could not be higher. There is scarcely a feature of the American health care system that does not depend on evidence-based trust in prescription drugs, ratified and enforced by the FDA,” Carpenter concludes.
(JAMA Intern Med. Published online October 28, 2013. doi:10.1001/jamainternmed.2013.9202. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor’s Note: Please see article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
HDL cholesterol controls blood glucose
Neuherberg, 30.10.2013. High density lipoprotein cholesterol (HDL), the so-called “good“ cholesterol improves blood glucose levels by enhancing skeletal muscle function and reducing adiposity, scientists of the Helmholtz Zentrum München report in the current issue of the renown American Heart Association Journal ‚Circulation‘.
Atherosclerotic cardiovascular disease rates are markedly increased in individuals with type 2 diabetes. One of the strongest independent predictors of cardiovascular disease in these patients is a low circulating level of high density lipoprotein (HDL) cholesterol and its major protein constituent apolipoprotein A-I (ApoA-I). An international team of scientists led by Dr. Susanna Hofmann from the Institute of Diabetes and Regeneration Research at the Helmholtz Zentrum München (HMGU), Partner of the German Center for Diabetes Research (DZD), and Dr. Maarit Lehti from the LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland, have now determined that normal circulating HDL levels are required for proper skeletal muscle metabolism and function. In their study, Hofmann and her team observed that without ApoA-I, burning of calories is reduced in skeletal muscle resulting in increased blood glucose and weaker muscle function. The scientists then determined that HDL cholesterol and its protein ApoA-I both enhance usage of glucose and calories inside muscle cells. Raising HDL and ApoA-I levels in animal models resulted in protection against hyperglycemia and age-related symptoms such as decline of muscle performance or fat mass gain. Improved calorie burning in mitochondria (the “power plants” in each cell) was further indicated by a marked reduction of circulating Fibroblast Growth Factor 21, a novel biomarker for mitochondrial dysfunction. “Our results link for the first time low HDL-cholesterol with impaired use of glucose and burning of calories in type 2 diabetes. ApoA-I analogues are now clinically tested for the prevention and regression of atherosclerosis. Based on our findings described herein, these analogs may offer underappreciated potential for therapeutic opportunities in diabetes”, explains Hofmann, who investigates interactions of fat and glucose metabolism with her international team. She adds: “Most importantly, our results are highly relevant for women with type 2 diabetes. Their risk for cardiovascular diseases compared to men with type 2 diabetes is significantly increased, because these women have low concentrations of HDL-cholesterol and ApoA-I.” The numerous conditions associated with overweight and obesity, such as T2D, are among the major widespread diseases in Germany. They are the focus of the research at the Helmholtz Zentrum München.
Oligomeric proanthocyanidin suppresses the death of retinal ganglion cells
The death of retinal ganglion cells is a hallmark of many optic neurodegenerative diseases such as glaucoma and retinopathy. Oxidative stress is one of the major reasons to cause the cell death. A latest study, published in the Neural Regeneration Research (Vol. 8, No. 25, 2013), has shown that grape seed extract can protect retinal ganglion cells against oxidative stress-induced apoptosis. In this study, Prof. Kwok-Fai So, an academician of Chinese Academy of Sciences, and Prof. Daxiang Lu from Jinan University, China show that oligomeric proanthocyanidin, enriched in grape seeds, has a protective effect on retinal ganglion cells against oxidative stress-induced injury, as confirmed by using both RGC-5 cell lines and retinal explant culture. These findings imply a potential application of oligomeric proanthocyanidin in the clinical treatment of many neural diseases, from glaucoma, ischemia to neurodegenerative disease
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.
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