20090903-71

A virtual-reality simulator promises safer operations and better training.

MIT Technology Review, September 2, 2009, by Tim Hornyak  —  A new simulator that lets neurosurgeons rehearse before operating–like pilots on a flight simulator–could revolutionize how doctors train for and handle brain surgery.

NeuroTouch, the prototype simulator developed by Canada’s National Research Council (NRC) and several other research groups, gives surgeons a dry run in virtual reality before entering the operating room, potentially reducing mistakes.

First, patient data from functional magnetic resonance imaging (fMRI) is rendered into a 3-D, high-resolution model of an individual’s brain. After the model is loaded into the system, doctors can touch and manipulate tumors and other virtual objects on screens in real time using a physical instrument resembling a scalpel. The instrument has six degrees of freedom and re-creates the force-feedback of the real tool and the varying resistance of tissue in brain regions with differing toughness. Meanwhile, photo-realistic on-screen imagery shows the simulated surgery, including bleeding and pulsing gray matter.

“This is the first simulator to fully integrate medical image processing, material models, finite element modeling, graphics, and haptics technologies to create a patient-specific simulation,” says Ryan D’Arcy, an NRC neuroscientist who helped develop NeuroTouch. “One other notable feature is the incorporation of functional brain mapping data from fMRI.” This allows critical brain regions, such as speech areas, to be imaged more accurately, D’Arcy says.

The $9.1 million, three-year project to develop a neurosurgery simulator began in April 2008 and involves some 50 clinicians and engineers from across Canada. The project marked a milestone last month when surgeons in Halifax, Nova Scotia, used it to rehearse before operating on a 48-year-old woman with a benign tumor near the speech center of her brain. The five-hour operation was successful, and the woman was discharged the following day. Though the procedure was relatively simple, it was the first time a simulator had been used to run through such an operation.

Lead surgeon David Clarke of Halifax’s Queen Elizabeth II Health Sciences Center praised the prototype for being very realistic. “The surgery team went in there with a knowledge and confidence that we could not otherwise have,” Clarke said after the surgery. “I think that that is not only good in terms of discussions with patients beforehand, but is good for their overall surgical outcome.”

As brain operations become less invasive but more complex, younger surgeons may be better trained using a simulator, says Rolando Del Maestro of the Montreal Neurological Institute and Hospital, who was involved with the project. “We neurosurgeons are going to be like simulator pilots, so we can find out if our skills are at a certain level,” says Del Maestro, who adds that the simulator might help accelerate training.

Abhijit Guha, a neurosurgeon at Toronto’s Hospital for Sick Children, who is unaffiliated with NeuroTouch, says that virtual surgery will never replace the real thing. “One weakness of the system is that it is based on archival MRI scans, which may not be valid as surgery proceeds due to brain and cerebrospinal fluid shifts,” Guha says. “Also, there is the judgment factor, especially when something goes wrong.”

A technical limitation of the prototype is that it can only represent tumors close to the surface of the brain, and surgeons can only use one hand. Development will continue through April 2011, however, and the final device will allow doctors to work on deep brain tumors with multiple surgical tools and both hands.

NRC plans to send prototypes to neurosurgery centers across Canada, and then transfer the technology to a commercial partner within two years. A commercial version could sell for $10,000 to $500,000, depending on its functions. “The package will include a PC-based planner for optimal surgical corridor selection as well as a trainer for surgical tasks and typical surgical procedures,” says NRC’s Robert DiRaddo, who led development. “The two will be integrated into a rehearsal system for patient-specific use.”

“The objective from the outset has been to commercialize the neurosurgical simulator,” D’Arcy says. “The goal is to put the simulator in clinics, hospitals, and teaching centers around the world, but there is a lot of work yet to be done.”

University of CaliforniaSanta Barbara, September 2, 2009  —  . Biological Mechanism For Delivering Nanoparticles Into Tissue: Potential Drug Delivery System. ScienceDaily  

– Scientists at UC Santa Barbara have discovered a potential new drug delivery system. The finding is a biological mechanism for delivery of nanoparticles into tissue. The results are published in the Proceedings of the National Academy of Sciences.

“This work is important because when giving a drug to a patient, it circulates in the blood stream, but often doesn’t get into the tissue,” said senior author Erkki Ruoslahti, of the Burnham Institute for Medical Research at UCSB. “This is especially true with tumors.

“We believe this method will lead to better, more efficient delivery of drugs,” he said. In this study, the scientists used prostate cancer cells as their target, but the method could apply to any type of cell.

The scientists developed a peptide, a small piece of protein that can carry “cargo” for delivery into the cell. The cargo could be a nanoparticle, or even a cell. Riding on the peptide, the cargo gets out of the blood vessel and penetrates the tissue.

The drug is located at one end of the peptide. At the other is the “C terminal,” which has the “motif” — an amino acid sequence including arginine or lysine, that causes the tissue penetration. This terminal has to be open, the researchers found. The strict requirement for the C terminal led the group to coin a new name, the “C-end rule,” or CendR, pronounced “sender.”

Ruoslahti explained that another exciting aspect of the study is the discovery that viruses appear to use this “CendR” system to get into cells. “It’s a natural system,” he said. “We’re not quite clear what the exact function is, but viruses appear to take advantage of it.”

Ongoing research in the Ruoslahti lab is understanding how viruses use this system, and then working to develop inhibitors to prevent viruses from entering the cell.

The two first authors on the paper are Tambet Teesalu and Kazuki N. Sugahara, both of the Burnham Institute for Medical Research at UCSB. Third author Venkata Ramana Kotamraju, of the same institute, made the peptides. Ruoslahti is also affiliated with the Burnham Institute for Medical Research in La Jolla, Calif.

20090903-6

The top image shows a mixture of gold nanoparticles. The longer particles are called nanobones, and the smaller are nanocapsules. Bottom left: After the nanoparticles are hit with 800 nanometer wavelength infrared light, the nanocapsules melt and release their payload. Nanobones remain intact. Right: After the nanoparticles are hit with 1100 nanometer wavelength infrared light, the nanobones melt and release their payload. Nanocapsules remain intact. (Credit: Image / Andy Wijaya) 

MIT Technology Reviews, ScienceDaily.com  –  Using tiny gold particles and infrared light, MIT researchers have developed a drug-delivery system that allows multiple drugs to be released in a controlled fashion.

Such a system could one day be used to provide more control when battling diseases commonly treated with more than one drug, according to the researchers.

“With a lot of diseases, especially cancer and AIDS, you get a synergistic effect with more than one drug,” said Kimberly Hamad-Schifferli, assistant professor of biological and mechanical engineering and senior author of a paper on the work that recently appeared in the journal ACS Nano.

Delivery devices already exist that can release two drugs, but the timing of the release must be built into the device — it cannot be controlled from outside the body. The new system is controlled externally and theoretically could deliver up to three or four drugs.

The new technique takes advantage of the fact that when gold nanoparticles are exposed to infrared light, they melt and release drug payloads attached to their surfaces.

Nanoparticles of different shapes respond to different infrared wavelengths, so “just by controlling the infrared wavelength, we can choose the release time” for each drug, said Andy Wijaya, graduate student in chemical engineering and lead author of the paper.

The team built two different shapes of nanoparticles, which they call “nanobones” and “nanocapsules.” Nanobones melt at light wavelengths of 1,100 nanometers, and nanocapsules at 800 nanometers.

In the ACS Nano study, the researchers tested the particles with a payload of DNA. Each nanoparticle can carry hundreds of strands of DNA, and could also be engineered to transport other types of drugs.

In theory, up to four different-shaped particles could be developed, each releasing its payload at different wavelengths.

Other authors of the paper are Stefan Schaffer and Ivan Pallares, who were National Science Foundation REU (Research Experiences for Undergraduates) summer students through the MIT Department of Biological Engineering in 2008.

American Thoracic Society  –  Aerosol delivery of antibiotics via nanoparticles may provide a means to improve drug delivery and increase patient compliance, thus reducing the severity of individual illnesses, the spread of epidemics, and possibly even retarding antibiotic resistance.

Delivery of antibiotics via nanoparticles has shown promise as a drug delivery mechanism, particularly for controlled release or depot delivery of drugs to decrease the number of doses required to achieve a clinical effect. The effectiveness of this delivery mechanism has not been confirmed directly either in infection models or in patients, but according to new data to be presented on Tuesday, May 19, at the American Thoracic Society’s 105th International Conference in San Diego, this delivery technique appears indeed promising.

Carolyn L. Cannon, M.D., Ph.D. from Washington University School of Medicine, and colleagues from the Center for Silver Therapeutics Research at the University of Akron in OH investigated the efficacy of nanoparticle-encapsulated silver-based antibiotics for treating pulmonary infections in a mouse model of pneumonia. Treatment with antibiotic-laden nanoparticles effectively eliminated respiratory infections in mice that had been inoculated with Pseudomona aeroginosa, a common bacterial species that often infects the respiratory tract in humans, particularly immunocompromised patients, ventilated patients or those with cystic fibrosis.

Infected mice that inhaled aerosolized nanoparticles encapsulating silver carbene complexes (SCCs), a novel class of silver-based antimicrobials with broad-spectrum activity, showed a significant survival advantage over the control mice that received nanoparticles without the SCCs. Treated mice also had decreased lung bacterial burden and spread, compared to the control mice. Moreover, the treatment with nanoparticles occurred once every 24 hours, a regimen that is known to increase compliance in human patients, versus the usual dosing interval of inhaled antibiotics for P. aeruginosa, which is twice daily.

“We were surprised and thrilled to see a 100 percent survival advantage in mice treated daily with SCC22-loaded nanoparticles at doses significantly lower than those used to achieve a similar survival advantage in twice-daily dosing of unencapsulated SCC22. During a 72 hour period, all of the infected control mice died, whereas all of the mice that received just two doses of SCC22-loaded nanoparticles spaced 24 hours apart survived.”

“My collaborators, Wiley Youngs, Ph.D., and Yang Yun, Ph.D., and I are eager to complete toxicity studies that would enable us to start clinical trials,” said Dr. Cannon. “While the mouse studies are tantalizing, the goal that propels our research is realizing the promise of these novel antibiotics and delivery mechanisms through an analogous survival advantage in patients.”

20090903-2

The tools they are working on have extraordinary potential, from sensing and eliminating a single cancer-causing tumor cell in an otherwise healthy body, to detecting traces of drugs, explosives, and other hazardous materials at concentrations of parts-per-trillion.

Some similar results may be achievable already in a laboratory. “Given a fully-equipped laboratory and enough time, you can detect almost anything,” says Kevin Plaxco, Professor of Chemistry and Biochemistry. What sets UCSB’s latest research apart is the goal of providing the same or better information much faster and much more conveniently-in many cases using mobile, hand-held devices.

“What has been a slow, lab-bound approach, we want to convert to less than 15 minutes-that’s typically how long, for example, someone has with their doctor-and hand held.” Plaxco says.

While that’s a clear reference to the medical implications of this biotechnology, potential applications are very much broader: researchers are working on projects that will impact food safety, the environment, industry, security, the military and more.

According to Martin Moskovits, former Dean of Science and currently Professor of Chemistry and Biochemistry, the need for detection and diagnostics is not new – he says it was an issue even back in the Middle Ages. As modern life becomes ever faster and more complex, however, detection and diagnostics are racing to keep pace.

Biotechnology has also become a rapidly evolving field in part because of the increasing numbers and varieties of hazards out there-infectious diseases, security and military threats, chemical and biological agents-that we need to be aware of so they can be dealt with or avoided.

20090903-3

Professor Kevin Plaxco and his research team are focused on studying detection devices more sensitive and still with hand-held convenience and price.

The interdisciplinary research teams working in this area draw from chemical, electrical, and mechanical engineering, computer science, and materials; and chemistry, biochemistry, physics, and molecular biology. The teams include scientists from UCSB’s Institute for Collaborative Biotechnologies (ICB), Materials Research Laboratory (MRL,) and the California NanoSystems Institute (CNSI).

ICB, a UCSB-led collaboration with the Massachusetts Institute of Technology (MIT) and the California Institute of Technology (Caltech), acts as the base for some 200 faculty members and researchers. Seeking to adapt and replicate some of the processes and biomolecular behaviors found in the natural world, many of these researchers are working at or close to the nanoscale.

Using state-of-the-art equipment available at UCSB, they are developing more easily managed and controlled ways of detecting and analyzing a broad range of molecules and microbes found in water, blood, air and food.

This process of separating, identifying, and counting the components in such materials invites a number of possible approaches, including many based on biological recognition. Examples of this include the binding of one strand of DNA to its complement (to form a double helix), the binding of an antibody to the virus it neutralizes, both of which are high affinity and specificity.

Other approaches depend on the specific optical (spectroscopic) signatures produced when target molecules bind to specially prepared nano surfaces, and the concentrated light emitted when specific nano particles are brought into close contact via a bio-recognition event.

Moskovits has been part of a team researching how these electrical and light signals can be used to detect and analyze even low concentrations of certain molecules.

The technology has clear medical potential-molecules being constantly released by the body in breath and perspiration, for example, could tell a doctor much about a patient’s health. Initially, however, Moskovits has his sights set on detecting explosives.

He and Carl Meinhart, Associate Professor of Mechanical Engineering and Director of UCSB’s Microfluidics Laboratory, are the principals of SpectraFluidics. The Goleta-based company, launched about a year ago, aims to develop inexpensive yet sensitive and highly accurate means of instantly detecting airborne explosives molecules. SpectraFluidics’ hand-held and stationary sensors will feature onboard computers with programs set to recognize only the specific light or electrical patterns caused by the presence of the target molecules.

Moskovits sees a security role for such sophisticated technology, at places like airports, and a military role during conflicts, such as the wars in Iraq and Afghanistan, where the accurate sensing of trace molecules in the air could, for instance, alert troops to roadside bombs.

“Now we need about one billion cells grouped together before we can see them and detect a tumor,” explains Daugherty.  “Our plan is to drop that number down by a factor of ten or 100 or more.”

SpectraFluidics is just one of a burgeoning number of UCSB-based biotech start-ups, many of them in the Santa Barbara area, looking for ways to transform an idea that works in the laboratory into a piece of technology that people are willing to buy.

Another local venture, Nanex, working in conjunction with ICB researchers, is developing what it describes as “a lab-on-a-chip” solution for medical diagnostics at hospitals, clinics and other health facilities.

“Our solution is a low cost, low power, lightweight instrument, well-suited for point-of-care detection of pathogens and genetic markers,” says the company website, describing a sensor equipped for a range of bio-assays and molecular diagnostics.

The road to market can be a long, difficult, and expensive journey. Plaxco says research into biotechnology devices has been going on for more than 50 years, but little has so far seen the commercial light of day: the best example that has is the blood glucose monitor for diabetics.

Plaxco has been working alongside Professor of Physics and Nobel laureate Alan Heeger, and H. Tom Soh, Associate Professor of Materials and of Mechanical Engineering, on biomolecular sensors designed for real-time detection at the point of care. The three men also collaborated closely with Nanex on product development.

Their point of departure is that current methods for the detection of pathogens are cumbersome, laboratory-bound procedures that typically require days to return an answer.

To address this problem, “we are developing a reagentless, electronic technology that can detect these materials in seconds with a convenient, hand-held electronic device,” Plaxco says.

Sumita Pennathur, Assistant Professor of Mechanical Engineering, is working in the areas of biometric identification and microfluidics, researching the development of biosensors that could be used to detect and diagnose a range of diseases.

Speaking from a conference on molecular bioseparations held recently in Boston, she described a hand-held device she hopes will isolate and identify DNA from a cheek swab in as little as 30 seconds. Such technology could prove valuable in settings as diverse as military checkpoints and medical clinics.

Though Pennathur estimates her research is still three to four years away from commercial development, she sees potential in such areas as AIDS and cancer research, detection of toxic chemicals, and monitoring water quality.

She’s a big fan of the collaborative environment at UCSB, especially the seamless overlapping within the ICB. “We talk a lot amongst ourselves; we also hold social events every quarter with the students, to get them sharing ideas as well.

20090903-4

Professor Patrick Daugherty and his collegues at CytomX Therapeutics (an early stage, privately-funded biotechnology company developing proteolytically-activated biotherapeutics based on UCSB research) have crafted a molecule that is activated by protease at cancer tissue binding sites. After clipping the mask molecule on the antibody, binding occurs on the target molecule. This specificity enables direct delivery of therapeutic agents to the desired site.

“It all helps spread knowledge and is so easy to do at UCSB where everyone is very helpful and accessible. It’s an awesome atmosphere.”

Plaxco shares that enthusiasm. “The ICB has helped us create a strong community of disparate research groups,” he says. “It’s also been a life-saving source of funding.”

Those kinds of responses are music to the ears of David Gay, the ICB’s director of technology, who sits at the interface between the institute’s principal funder–the Army Research Office–and academia and industry.

The Army began a five-year funding commitment in August 2003, and has since renewed for a further five years. Gay states that the institute received $44 million during the first five-year period. The Army’s budget for ICB in the second five years, fiscal years 2009 through 2013, totals $84 million, of which $15 million has been received so far for FY 2009.

In both cases, the amounts have gradually increased as the Army responded positively to the results coming out of the ICB. “The point is, we are delivering,” says Gay.

“Our mission is to accelerate innovation,” he added, pointing to the transition of technology to the marketplace through young companies like CytomX Therapeutics, Cynvenio Biosystems, and Sirigen.

Both CytomX, based in Goleta, and Cynvenio, located in Westlake, were founded by Patrick Daugherty, Associate Professor of Chemical Engineering, Soh, and Heeger.

Cynvenio focuses on advanced instrumentation for bioseparation and cell-sorting applications, using microfluidics technology. “Integrating multiple steps of a complex assay, all on a chip, to obtain highly sensitive and error-free results rapidly and inexpensively … that’s the revolution that’s coming,” predicts Soh.

His work at UCSB and Cynvenio was recently recognized at the annual conference of the Association for Laboratory Automation, in Palm Springs, where he won the 2009 ALA Innovation award for the most creative solutions to some of today’s most important problems in biotechnology.

20090903-5

CytomX is addressing the early detection and treatment of tumors and vulnerable plaque. The company hopes to provide diagnostic tools for people at risk from cancerous tumors, and from heart attacks or strokes caused when plaque from artery walls ruptures and enters the bloodstream.

Their teams are using molecular and cellular engineering to achieve this. They have learned how to manipulate certain molecules, blocking their normal function and instead giving them the ability to sniff out and bind only with molecules indicating tumors or at-risk plaque.

These pre-programmed molecules, engineered in vitro, are introduced into the patient’s bloodstream and the results scanned using a magnetic resonance imaging (MRI) machine.

“Now we need about one billion cells grouped together before we can see them and detect a tumor,” explains Daugherty. “Our plan is to drop that number down, by a factor of ten or 100 or more.” Finding tumors at such an early stage would enable much earlier treatment and far better patient prognoses.

Having proved the concept, Daugherty says the science is now being tested in mice. Many more animal and human trials lie ahead, but he hopes a commercial product could be ready for approval in less than three years.

For Plaxco and the others, the real value in all this research is making products that help people: “Our focus is on things that we think will directly improve people’s health and safety,” he stated.

Professor Kimberly Turner, Chair of the Department of Mechanical Engineering, shares this vision, and believes biotechnology is going to revolutionize the future of healthcare.

“The technology has matured to the point where it’s right for diagnostics, especially medical diagnostics,” she says. “I think this is going to be a huge market in the next five to 10 years.”

Turner has been working on the ultra-sensitive detection of carbon monoxide and other gases, developing technology that could potentially also alert users to a range of hazards from toxic chemicals and explosives to food-borne pathogens.

She sees many advantages for this type of detection and diagnostic technology: it’s small, easy to use, works fast, and is sufficiently cheap to manufacture that units could be disposable.

She believes the low cost and high convenience will have a major impact on procedures like lab tests and cancer screening which can become “much simpler and cheaper”.

Turner also foresees the day when the technology will be readily available off the retail shelf, enabling people to buy self-testing kits at the drug store and do many health-related tests themselves.

20090903-1

A mouse tumor treated with an aptamer-siRNA combination (right) shows many dead areas (indicated by the asterisks), whereas an untreated tumor (left) is still largely intact. Delivering siRNA successfully to specific cells has been challenging. UI researchers modified siRNA so that it could be injected into the bloodstream and impact only targeted cells. (Credit: University of Iowa)

University of Iowa, September 2, 2009 – Small interfering RNA (siRNA), a type of genetic material, can block potentially harmful activity in cells, such as tumor cell growth. But delivering siRNA successfully to specific cells without adversely affecting other cells has been challenging.

University of Iowa researchers have modified siRNA so that it can be injected into the bloodstream and impact targeted cells while producing fewer side effects. The findings, which were based on animal models of prostate cancer, also could make it easier to create large amounts of targeted therapeutic siRNAs for treating cancer and other diseases. The study results appeared online Aug. 23 in the journal Nature Biotechnology.

“Our goal was to make siRNA deliverable through the bloodstream and make it more specific to the genes that are over expressed in cancer,” said the study’s senior author Paloma Giangrande, Ph.D., assistant professor of internal medicine and a member of Holden Comprehensive Cancer Center.

In previous research completed at Duke University, Giangrande’s team showed that a compound called an aptamer can be combined with siRNA to target certain genes. When the combined molecule is directly injected into tumors in animal models, it triggers the processes that stop tumor growth. However, directly injecting the combination into tumors in humans is difficult.

In the new study, the researchers trimmed the size of a prostate cancer-specific aptamer and modified the siRNA to increase its activity. Upon injection into the bloodstream, the combination triggered tumor regression without affecting normal tissues.

Making the aptamer-siRNA combination smaller makes it easier to produce large amounts of it synthetically, Giangrande said.

The team also addressed the problem that large amounts of siRNA are needed since most of it gets excreted by the kidneys before having an effect. To keep siRNA in the body longer and thereby use less of it, the team modified it using a process called PEGlyation.

“If you want to use siRNA effectively for clinical use, especially for cancer treatment, you need to deliver it through an injection into the bloodstream, reduce the amount of side effects and be able to improve its cost-effectiveness. Our findings may help make these things possible,” Giangrande said.

Although the current study focused on prostate cancer, the findings could apply to other cancers and diseases. Giangrande said the next step is to test the optimized aptamer-siRNA compound in a larger animal model.

Other researchers who contributed significantly to the study included James McNamara, Ph.D., and Anton McCaffrey, Ph.D., both UI assistant professors of internal medicine.

WebMD.com, September 2, 2009

Medical Authors: Dennis Lee, MD and Jay W. Marks, MD
Medical Editor: William C. Shiel, Jr., MD, FACP, FACR

What is red yeast rice?

Red yeast rice is rice that has been fermented by the red yeast, Monascus purpureus. It has been used by the Chinese for many centuries as a food preservative, food colorant (it is responsible for the red color of Peking duck), spice, and an ingredient in rice wine. Red yeast rice continues to be a dietary staple in China, Japan, and Asian communities in the United States, with an estimated average consumption of 14 to 55 grams of red yeast rice per day per person.

Red yeast rice also has been used in China for over 1,000 years for medicinal purposes. Red yeast rice was described in an ancient Chinese list of drugs as useful for improving blood circulation and for alleviating indigestion and diarrhea.

Recently, red yeast rice has been developed by Chinese and American scientists as a product to lower blood lipids, including cholesterol and triglycerides.

What is the present status of red yeast rice?

Small scale studies using pharmaceutical-grade red rice yeast have continued to demonstrate efficacy and safety. However, in the United States it is no longer legal to sell supplements of red yeast rice that contain more than trace amounts of cholesterol lowering substances. For example, the active ingredients of red rice yeast have been removed from Cholestin marketed in the United States. (Hypocol, another product containing red yeast rice is no longer being sold in the United States.)

The reasons the Food and Drug Administration (FDA) has ruled that it is illegal to sell red yeast rice that contains more than trace amounts of the cholesterol-lowering substances and to promote red yeast rice for lowering cholesterol levels.

  • First, statin drugs are associated with muscle and kidney injury when used alone or combined with other medications. There is concern that patients who already take statin drugs with or without these other medications may increase their risk of muscle or kidney injury.
  • Second, the FDA considers the products containing red yeast rice with high levels of cholesterol lowering substances to be new, unapproved drugs for which marketing violates the Federal Food, Drug, and Cosmetic Act.

What are the different preparations of red yeast rice?

There are three major preparations of red yeast rice:

  • 1. Zhitai,
  • 2. Cholestin or Hypocol, and
  • 3. Xuezhikang.

Zhitai

Zhitai is produced by the fermentation of a mixture of different strains of Monascus purpureus on whole grain rice. Zhitai contains mainly rice and yeast, but is mostly rice by weight.

Cholestin or HypoCol

Cholestin or HypoCol is produced by the fermentation of selected strains of Monascus purpureus, using a proprietary process that produces a certain concentration of monacolin K (monacolin K is lovastatin, which is believed to be the major cholesterol-lowering ingredient).

Xuezhikang

Xuezhikang is produced by mixing the rice and red yeast with alcohol and then processing it to remove most of the rice gluten. Xuezhikang contains 40% more cholesterol-lowering ingredients than Cholestin or Hypocol.

In Singapore, red yeast rice is available as Hypocol (NatureWise, Wearnes Biotech & Medicals (1998) PTE LTD).

What is the composition of HypoCol and Cholestin?

At one time, Cholestin contained red yeast rice, and at that time scientists at Pharmanex and the UCLA Center for Human Nutrition analyzed the properties Cholestin. The composition by weight is:

  • starch (73%),
  • protein (5.8%)
  • moisture (3%-6%),
  • unsaturated fatty acids (1.5%),
  • monacolins (0.4%),
  • ash (3%), and
  • trace amounts of calcium, iron, magnesium, and copper.

There are no additives, preservatives, heavy metals, or toxic substances, such as citrinic acid.

In 1977, Professor Endo in Japan discovered a natural cholesterol-lowering substance that is produced by a strain of Monascus yeast. This substance inhibits HMG-CoA reductase, an enzyme that is important for the production of cholesterol in the body. Professor Endo named this substance moncacolin K. Since then, scientists have discovered a total of eight monacolin-like substances that have cholesterol-lowering properties.

Monacolin K is lovastatin, the active ingredient in the popular statin drug, lovastatin (Mevacor), which is used for lowering cholesterol. Lovastatin also is believed to be the main cholesterol-lowering ingredient in HypoCol. The lovastatin in Mevacor is highly purified and concentrated, the lovastatin in HypoCol is not. Thus, they contain much lower concentrations of lovastatin than Mevacor. For example, each 600-mg capsule of Cholestin contains less than 2.4 mg of lovastatin (when this ingredient was contained in the product), whereas tablets of Mevacor contain 10 mg or more of this ingredient.

Because none of the components are purified and concentrated, HypoCol and Cholestin (marketed outside of the US) contain a mixture of the eight yeast-produced monacolins, unsaturated fatty acids, and certain anti-oxidants. Some scientists believe that these other monacolins, unsaturated fatty acids, and anti-oxidants may work together favorably with lovastatin to enhance its cholesterol-lowering effects, as well as its ability in lowering triglycerides and increasing HDL cholesterol. (HDL is considered the “good” form of cholesterol since high levels of HDL cholesterol protect against heart attacks.) Further studies in animals and humans will be necessary to test these theories.

How effective are HypoCol, Cholestin, and Xuezhikang in lowering lipids?

Chinese scientists conducted most of the animal and human studies on this issue, using either Zhitai or Xuezhikang. The results of some 17 studies involving approximately 900 Chinese subjects with modestly elevated cholesterol levels have been published. In eight of these studies, there was a control group that received a placebo (a pill with no active ingredients) for comparison purposes. In nine of the studies, there was no placebo control group.

These studies consistently showed that Zhitai and Xuezhikang:

  • lower total cholesterol (by an average of 10% to 30%),
  • lower LDL cholesterol (by an average of 10% to 20%),
  • lower triglycerides (by an average of 15% to 25%), and
  • increase HDL (by an average of 7% to 15%).

Scientists at the UCLA Center for Human Nutrition studied Cholestin in a 12-week, double blind, placebo-controlled trial involving 83 American adults with borderline-high to moderately elevated cholesterol. They found that Cholestin (when red yeast rice was an ingredient in this product) reduced total cholesterol, LDL cholesterol, and triglyceride levels but had no effect on HDL cholesterol. This study was published in the American Journal of Clinical Nutrition (1999; 69:231-7).

Lowering LDL and increasing HDL cholesterol prevents atherosclerosis (a build-up of plaque) of the heart’s arteries. Since atherosclerosis causes heart attacks, lowering the LDL and increasing HDL cholesterol should lower the risk of heart attacks. In fact, several large, long-term, placebo-controlled clinical trials have shown clearly that lowering LDL cholesterol with diet and statin drugs [pravastatin (Pravachol) , lovastatin (Mevacor), and simvastatin (Zocor) reduces the risk of heart attacks. No large, long-term studies of red yeast rice products for the prevention of heart attacks have yet been conducted. However, animal studies are underway at UCLA comparing red yeast rice to a statin drug (such as Mevacor) for the prevention and treatment of atherosclerosis.

How safe are red yeast rice products?

Animal studies have been conducted in China using high doses of red yeast rice products. No damage to the kidneys, liver, or other organs were demonstrated in these studies.

Human trials in China and in the United States reported only rare and minor side effects of heartburn or indigestion with the use red yeast rice products. No liver, kidney, or muscle toxicity has been reported.

However, human trials in the United States and China have generally lasted only a few weeks to a few months. Thus, conclusive proof of long term safety (over a period of many years) will have to await further data (such as from data received after the products have been marketed or long-term clinical trials).

Scientists conducting the studies generally believe that red yeast rice is safe in the long-term since it has been a food staple for thousands of years in Asian countries without reports of toxicity. They attribute the safety of red yeast rice products to the process of preparation that does not involve the isolation and concentration of a single ingredient. Although it is true that isolation and concentration enhance the potency of a single ingredient, these factors also increase the risk of side effects.

Are there any precautions in consuming red yeast rice products?

Not all red yeast rice products contain the same concentrations of the cholesterol-lowering ingredients. Moreover, it is illegal in the United States to sell red yeast rice products that contain more than trace amounts of cholesterol lowering substances. Therefore, the red yeast rice products that are available in the United States do not contain levels of cholesterol lowering substances that are likely to cause side effects. Nevertheless, certain products also may contain unacceptably high levels of an undesirable and toxic substance called citrinic acid.

Who are suitable candidates for red yeast rice products?

There is not yet consensus among scientists and doctors as to the role, if any, of red yeast rice in treating elevated cholesterol. Therefore a doctor familiar with a patient’s personal medical condition and his/her family history of heart diseases should be prescribing cholesterol-lowering measures. Generally in the United States, when diet, weight loss, and exercise are insufficient in lowering cholesterol to optimal levels, many doctors recommend using a statin drug since large long-term trials have consistently shown that statins [such as pravastatin (Pravachol), simvastatin (Zocor), lovastatin (Mevacor), and atorvastatin (Lipitor)] are safe and effective in lowering LDL cholesterol and decreasing the risk of heart attacks and strokes. Although similar studies are not available for red yeast rice products, given the minimal amounts of cholesterol lowering substances that they are allowed to contain in the U.S., it would be expected that legal red yeast rice products would not be very effective at lowering cholesterol levels.

Who are not suitable candidates for red yeast rice?

Patients with moderate to severe cholesterol abnormalities, and patients who are at high risk of developing heart attacks or strokes are not candidates for red yeast rice. Examples of patients that are at high risk of heart attacks include patients who had prior heart attacks and strokes, patients with diabetes mellitus, and patients with atherosclerosis in the arteries that supply blood to the brain and to the extremities (peripheral artery disease). In these patients, red yeast rice containing legal amounts of cholesterol lowering substances (along with weight loss, diet, and exercise) is not potent enough to achieve the degree of cholesterol lowering desired.