Diane Wysowski of the FDA’s division of drug risk asessment said researchers should check into potential links between so called bisphosphonate drugs and cancer. In a letter in Thursday’s New England Journal of Medicine, Wysowski said since the initial marketing of Fosamax, known generically as alendronate, in 1995, the FDA has received 23 reports in which patients developed esophageal tumors.
Typically, two years lapsed between the start of the drug and the development of esophageal cancer. Eight patients died, she reported. In Europe and Japan, 21 cases involving Fosamax have been logged, with another six instances where Procter & Gamble’s Actonel or risedronate and Didronel or etidronate. Six of those people died.
Esophagitis, which is an inflammation of the lining of the tube carrying food to the stomach, is already known to be a side effect of the drugs.
Multiple sclerosis remains a cruel medical mystery. It strikes in the prime of life and runs an unpredictable course that can end in total disability. Scientists are a long way from halting the disease entirely, but several promising drugs are in late-phase clinical trials and experts anticipate better lives for patients in the near future.
“We will see many new drugs on the market and many new options for patients,” says Dr. Diego Centonze, a neurologist at Tor Vergata University in Rome, who is running clinical trials for three new experimental compounds, including one called fingolimod that is the first oral MS drug to move to Phase 3 clinical trials.
In the early 1990s, there were no Food and Drug Administration-approved therapies for MS on the market. Today, there are at least half a dozen, and Centonze expects as many as eight or nine by 2010.
But there are still many challenges, says Dr. Ari Green, assistant director of the multiple sclerosis center at UC San Francisco, which also is running drug company-sponsored trials. None of the approved drugs is ideal, and each of the new experimental drugs has significant adverse side effects.
MS is an autoimmune disease: The body’s immune system attacks some of its own tissues. The common form, known as relapsing-remitting, begins when disease-fighting lymphocytes launch an attack on the brain and spinal cord. These relapses cause short-term inflammation and symptoms such as numbness, but eventually lead to a progressive decline of the nervous system.
The less common form of MS — primary progressive — doesn’t manifest itself with acute attacks, although patients still exhibit neurodegeneration, leading to fatigue, pain, problems with walking and balance, dizziness and bladder and bowel dysfunction.
Currently approved drugs primarily work by reducing the activity of lymphocytes or reducing their ability to travel from the blood into the nervous system. Some of the new ones do that too — while others function in different ways.
The first drugs to gain approval in the mid-1990s were interferon beta-1b (Betaseron), interferon beta-1a (Avonex or Rebif) and glatiramer acetate (Copaxone). Because they have minimal side effects (such as flu-like symptoms) they are used as a first line of defense. But they are only moderately effective, says Dr. Rhonda Voskuhl, director of the UCLA multiple sclerosis program. Patients “fail them, and then move on” to more powerful drugs such as natalizumab (Tysabri) and mitroxantrone.
Mitroxantrone, approved in 2000, is a chemotherapeutic drug that suppresses the immune system and can lead to leukemia or heart damage.
Natalizumab (Tysabri), which received accelerated FDA approval in 2004 and is considered the most effective drug available today, was taken off the market in February 2005 after three patients in clinical trials developed progressive multifocal leukoencephalopathy, a fatal viral disease. After an FDA review, it has been available under a special program in which patients are closely monitored for opportunistic infections.
On the horizon
There’s clearly a lot of room for improvement, which is one reason why doctors are excited about options on the horizon.
Fingolimod, originally developed to prevent organ rejection in transplant patients, blocks a signal that allows T-cell lymphocytes to cross into the brain. At the American Academy of Neurology meeting this year, researchers reported that 173 patients with a relapsing form of MS showed a decline in the relapse rate over 36 months from 0.31 relapses per year to 0.20, a 30% decrease in their relapse rate when they took fingolimod. In just six months, the number of patients with brain lesions decreased from an average of 2.2 per patient when taking the placebo down to 1.29. In addition, after 36 months, brain scans revealed that 89% of patients had no evidence of inflammation.
Fingolimod is promising not only for effectiveness but because it comes in pill form, Centonze says. “For patients that must receive injections every other day or every single day, the quality of life is really affected. Taking pills can change this.”
Another compound on the horizon is alemtuzumab (Campath), a monoclonal antibody designed and FDA-approved for fighting leukemia. In a trial of 334 patients published in October in the New England Journal of Medicine, researchers reported that the drug could reduce the relapse rate in early-stage MS patients by two-thirds relative to the standard MS drug interferon beta-1a.
UCSF’s Green says the findings are impressive because this is the first MS trial to compare a new drug to an approved compound rather than a placebo and yet “it still had a remarkable effect on reducing disease activity.”
Rituximab, an antibody that was designed for treating rheumatoid arthritis, is also being studied, in a clinical trial headquartered at UCSF. Rituximab is directed at the immune system’s B cells, rather than T cells that have been targeted by MS researchers since the 1970s.
Biology of MS
In February, a team led by Dr. Stephen Hauser of UCSF reported in the New England Journal of Medicine that in a 48-week trial of 104 patients, rituximab halved the number of patients experiencing relapses relative to a placebo. “It’s led to a whole new understanding of the biology of MS,” Green says. “There are now a ton of potential therapies that are going to be B-cell directed.”
But the downside of taking powerful modulators of the immune system are their serious side effects, including making patients more susceptible to infections and other chronic diseases. Two patients died after taking fingolimod, one with a brain infection and the other with shingles.
And in the alemtuzumab trial published in October, researchers reported that one-quarter of the patients developed an autoimmune disease attacking the thyroid and three developed an autoimmune disease of the blood platelets.
“Drugs like this are toxic,” Voskuhl says. “It’s a hard sell to people who are very young to expose them to drugs that have dramatic side effects.”
A larger problem with the current slate of therapeutics is that they address only the inflammation side of the disease. “But we now know for sure that neurodegeneration is not just caused by inflammation,” Centonze says.
As excited as he is about the burgeoning treatment options, he says, “Before judging the real quality of these drugs, you must treat many, many patients for several years.” Sources:Los Angles Times
Millions of private patients are taking medications that have never been reviewed by the US government for safety and effectiveness, an Associated Press investigation found. And taxpayers have shelled out at least $200 million since 2004 for the unapproved medications that are still covered under Medicaid, according to the analysis of federal data has found.
The availability of unapproved prescription drugs to the public may create a dangerous false sense of security. Dozens of deaths have been linked to them.
The medications date back decades, before the Food and Drug Administration tightened its review of drugs in the early 1960s. The FDA says it is trying to squeeze them from the market, but conflicting federal laws allow the Medicaid health program for low-income people to pay for them.
The AP analysis found that Medicaid paid nearly $198 million from 2004 to 2007 for more than 100 unapproved drugs, mostly for common conditions such as colds and pain. Data for 2008 were not available but unapproved drugs still are being sold.
The AP checked the medications against FDA databases, using agency guidelines to determine if they were unapproved. The FDA says there may be thousands of such drugs on the market. Medicaid officials acknowledge the problem, but say they need help from Congress to fix it.
In a highly critical report, a panel of scientists from government and academia said when the FDA completed a draft risk assessment of bisphenol A (BPA) last month, they did not take into consideration numerous studies that have linked the chemical to prostate cancer, diabetes and other health problems.
The scientists took the FDA to task for basing its safety decision on three industry-funded studies.
The report was written by a subcommittee panel of the FDA’s outside science board, experts who advise the FDA on complex issues. The panel concluded that the FDA’s margin of safety is “inadequate.”
The panel said the FDA also didn’t use enough infant formula samples and didn’t adequately account for variations among the samples.
Studies the FDA did not consider when making their assessment suggest that BPA could pose harm to children at levels at least 10 times lower than the amount the agency called safe. Another government agency, the National Toxicology Program, concluded that there is “some concern” that BPA alters development of the brain, prostate and behavior in children and fetuses.
Latin name: Monascus purpureus Other names: Hong Qu, red rice, red yeast Synonyms:
Alkaloids, angkak, anka, ankaflavin, Asian traditional fermentation foodstuff, astaxanthin, beni-koju, ben-koji, Chinese red yeast rice, citrinin, CRYR, dehydromonacolin K, dietary red yeast, dihydromeyinolin, dihydromonacolin K, dihydromonacolin L, DSM1379, DSM1603, ergosterol, flavonoids, GABA, glycosides, HMG-CoA reductase inhibitors, hon-chi, hong qu, hongqu, hung-chu, hydroxymethylglutaryl coenzyme A reductase, KCCM11832, koji, linoleic acid, lovastatin, M9011, mevinolin, monacolin hyroxyacid, monacolin J, monacolin K, monacolin K (hydroxyl acid form), monacolin L, monacolin M, monacolin X, Monascaceae (yeast family), monascopyridine A, monascopyridine B, monascopyridine C, monascopyridine D, monascorubramine, monascorubrin, Monascus , Monascus anka , Monascus purpureus fermentate, Monascus purpureus HM105, Monascus purpureus NTU568, Monascus purpureus Went rice, Monascus ruber , oleic acid, orange anka pigment, palmitoleic acid, Phaffia rhodozyma , red fermented rice, red koji, red leaven, red mould rice, red rice, red rice yeast, red yeast, red yeast rice extract, rice, RICE products, rubropunctamine, rubropunctatin, RYR, RYRE, saponins, statins, stearic acid, xuezhikang, Xue Zhi Kang, yellow anka pigment, zhitai, Zhi Tai.
Definition:
Red yeast rice, red fermented rice, red kojic rice, red koji rice, or ang-kak, is a bright reddish purple fermented rice, which acquires its colour from being cultivated with the mold Monascus purpureus. In Japan, it is known as beni-koji ( lit. “red koji”) or akakoji ( also meaning “red koji”) and in Taiwan it is sometimes also called âng-chau , in Taiwanese. Among the Hakka, it is known as fungkiuk. In China it is widely available under the brand name XueZhiKang, and in Singapore it is available as Hypocol.
Red yeast rice is sold in jars at Asian markets as a pasteurized wet aggregate, whole dried grains, or as a ground powder. It was a commonly used red food colouring in East Asian and Chinese cuisine prior to the discovery of chemical food colouring. It has also been used in Chinese herbal medicine.
Red yeast rice is the product of yeast ( Monascus purpureus ) grown on rice, and is served as a dietary staple in some Asian countries. It contains several compounds collectively known as monacolins, substances known to inhibit cholesterol synthesis. One of these, “monacolin K,” is a potent inhibitor of HMG-CoA reductase, and is also known as mevinolin or lovastatin (Mevacor®, a drug produced by Merck & Co., Inc).
Red yeast rice extract has been sold as a natural cholesterol-lowering agent in over the counter supplements, such as CholestinTM (Pharmanex, Inc). However, there has been legal and industrial dispute as to whether red yeast rice is a drug or a dietary supplement, involving the manufacturer, the U.S. Food and Drug Administration (FDA), and the pharmaceutical industry (particularly producers of HMG-CoA reductase inhibitor prescription drugs or “statins”).
The use of red yeast rice in China was first documented in the Tang Dynasty in 800 A.D. A detailed description of its manufacture is found in the ancient Chinese pharmacopoeia, Ben Cao Gang Mu-Dan Shi Bu Yi, published during the Ming Dynasty (1368-1644). In this text, red yeast rice is proposed to be a mild aid for gastric problems (indigestion, diarrhea), blood circulation, and spleen and stomach health. Red yeast rice in a dried, powdered form is called Zhi Tai. When extracted with alcohol it is called Xue Zhi Kang.
Red yeast rice has been used in China as a preservative, spice, and food coloring. It’s used to give Peking duck its characteristic red color and can also be an ingredient in fish sauce, fish paste, and rice wine. Red yeast rice is used in traditional Chinese medicine as a remedy for poor circulation, indigestion, and diarrhea.
Red yeast rice contains naturally-occurring substances called monacolins. Monocolins, particularly one called lovastatin, is believed to be converted in the body to a substance that inhibits HMG-CoA reductase, an enzyme that triggers cholesterol production. This is the way the popular statin drugs work.
Because of this action, red yeast rice products containing a higher concentration of monocolins have been developed and marketed as a natural product to lower cholesterol.
The problem is that the primary ingredient in these supplements, lovastatin, is also the active pharmaceutical ingredient in prescription drugs for high cholesterol such as Mevacor. In fact, lovastatin was originally derived from another type of red yeast called Monascus ruber.
Production:-
Red yeast rice is produced by cultivating Monascus purpureus on polished rice. The rice is first soaked in water until the grains are fully saturated. The raw soaked rice can then either be directly inoculated, or steamed for the purpose of sterilizing and cooking the grains prior to inoculation. Inoculation is done by mixing M. purpureus spores or powdered red yeast rice together with the processed rice. The mix is then incubated in an environment around room temperature for 3–6 days. During this period of time, the rice should be fully cultured with M. purpureus, with each rice grain turning bright red in its core and reddish purple on the outside.
The fully cultured rice is then either sold as the dried grain, or cooked and pasteurized to be sold as a wet paste, or dried and pulverized to be sold as a fine powder. China is the world’s largest producer of red yeast rice.
Due to the high cost of chemical dyes, some producers of red yeast rice have tried to adulterate their products with red dye #2 Sudan Red G (in Chinese).
Uses:
Culinary
The dried grain can be prepared and eaten in the same manner as white rice–a common practice among Asians. It can also be added to other foods.
Red yeast rice is used to colour a wide variety of food products, including pickled tofu, red rice vinegar, char siu, Peking Duck, and Chinese pastries that require red food colouring. It is also traditionally used in the production of several types of Chinese wine, Japanese sake (akaisake), and Korean rice wine (hongju), imparting a reddish colour to these wines.
Although used mainly for its colour in cuisine, red yeast rice imparts a subtle but pleasant taste to food.
Traditional Chinese Medicine
In addition to its culinary use, red yeast rice is also used in traditional Chinese herbology and traditional Chinese medicine. Its use has been documented as far back as the Tang Dynasty in China in 800 A.D. and taken internally to invigorate the body, aid in digestion, and remove “blood blockages”.
Modern Medicine
Red yeast rice when produced using the ‘Went’ strain of Monascus purpureus contains significant quantites of the HMG-CoA reductase inhibitor lovastatin which is also known as mevinolin, a naturally-occurring statin. It is sold as an over the counter dietary supplement for controlling cholesterol (See ref.: Medicine Net). There is strong scientific evidence for its effect in lowering blood levels of total cholesterol, low-density lipoprotein/LDL (“bad cholesterol”), and triglyceride levels (see below). Because an approved drug is identical to the molecule it is therefore regulated as a drug by the Food and Drug Administration (FDA).
In 1998, the U.S. district court in Utah allowed a product containing red yeast rice extract known as Cholestin to be sold without restriction, but this was reversed on appeal. (Moore, 2001) (see ref.: PDRhealth). Cholestin as a product continues to be marketed but no longer contains red yeast rice (RYR). Other companies sell red yeast rice products but most of them use a different strain of yeast or different growing conditions, resulting in RYR with a negligible statin content. The labeling on these new products often says nothing about cholesterol lowering. As late as August 2007, FDA noted supplements being sold containing significant lovastatin levels.(FDA, 2007)
In 2006 Liu et al published a meta-analysis of clinical trials (Chinese Med 2006;1:4-17). The article cited 93 published, controlled clinical trials (91 published in Chinese). Total cholesterol decreased by 35 mg/dl, LDL-cholesterol by 28 mg/dl, triglycerides by 35 mg/dl, and HDL-cholesterol increased by 6 mg/dl. Zhao et al reported on a four-year trial in people with diabetes (J Cardio Pharmacol 2007;49:81-84). There was a 40-50% reduction in cardio events and cardio deaths in the treated group. Ye et al reported on a four-year trial in elderly Chinese patients with heart disease (J Am Geriatr Soc 2007;55:1015-22). Deaths were down 32%. There is at least one report in the literature of a statin-like myopathy caused by red yeast rice (Mueller PS. Ann Intern Med 2006;145:474-5).
An article in the June 15, 2008, issue of the American Journal of Cardiology found that red yeast rice may provide benefits beyond those provided by statins. The researchers reported that the benefits seemed to exceed those reported with lovastatin alone.
ConsumerLab.com found large variation in the active compounds between red yeast rice supplements, and also found that some of them were contaminated with citrinin, a nephrotoxic mycotoxin. Evidence about the side effects of red yeast rice is limited, but it may have similar side effects to the drug lovastatin, which include kidney problems and other side effects.[4] Regular medical monitoring is needed to detect such effects.
Evidence:
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Uses based on scientific evidence :-
High cholesterol
Since the 1970s, human studies have reported that red yeast lowers blood levels of total cholesterol, low-density lipoprotein/LDL (“bad cholesterol”), and triglyceride levels. Other products containing red yeast rice extract can still be purchased, mostly over the Internet. However, these products may not be standardized and effects are not predictable. For lowering cholesterol, there is better evidence for using prescription drugs such as lovastatin…..GRADE: A
Coronary heart disease
Preliminary evidence shows that taking Monascus purpureus by mouth may result in cardiovascular benefits and improve blood flow. Additional study is needed before a firm recommendation can be made…GRADE: C
Diabetes
Early human evidence suggests the potential for benefits in diabetics. Additional study is needed before a firm recommendation can be made….GRADE C
Key to grades :- A: Strong scientific evidence for this use;
B: Good scientific evidence for this use;
C: Unclear scientific evidence for this use;
D: Fair scientific evidence against this use;
F: Strong scientific evidence against this use.
Regulation:-
Red yeast rice is classified as a dietary supplement by the FDA. Because of its similarity to the statin drugs, there is an ongoing legal debate about whether red yeast rice should be reclassified as a prescription drug rather than a dietary supplement.
Uses based on tradition or theory :-
The below uses are based on tradition or scientific theories. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.
Dosing:
The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.
Adults (18 years and older)
1,200 milligrams of concentrated red yeast powder capsules have been taken two times per day by mouth with food.
The average consumption of naturally occurring red yeast rice in Asia has been reported as 14-55 grams per day.
Children (younger than 18 years)
There is not enough scientific evidence to recommend red yeast for children.
Safety:
The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.
Allergies
There is one report of anaphylaxis (a severe allergic reaction) in a butcher who touched meat containing red yeast.
Side Effects and Warnings:-
There is limited evidence on the side effects of red yeast. Mild headache and abdominal discomfort can occur. Side effects may be similar to those for the prescription drug lovastatin (Mevacor®). Heartburn, gas, bloating, muscle pain or damage, dizziness, asthma, and kidney problems are possible. People with liver disease should not use red yeast products.
In theory, red yeast may increase the risk of bleeding. Caution is advised in patients with bleeding disorders or taking drugs that may increase the risk of bleeding. Dosing adjustments may be necessary. A metabolite of Monascus called mycotoxin citrinin may be harmful.
Pregnancy and Breastfeeding
Prescription drugs with similar chemicals as red yeast cannot be used during pregnancy. Therefore, it is recommended that pregnant or breastfeeding women not take red yeast.
Interactions:-
Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.
Interactions with Drugs
There are not many studies of the interactions of red yeast rice extract with drugs. However, because red yeast rice extract contains the same chemicals as the prescription drug lovastatin, the interactions may be the same. Fibrate drugs or other cholesterol-lowering medications may cause additive effects or side effects when taken with red yeast. Alcohol and other drugs that may be toxic to the liver should be avoided with red yeast rice extract. Taking cyclosporine, ranitidine (Zantac®), and certain antibiotics with red yeast rice extract may increase the risk of muscle breakdown or kidney damage.
Certain drugs may interfere with the way the body processes red yeast using the liver’s “cytochrome P450” enzyme system. Inhibitors of cytochrome P450 may increase the chance of muscle and kidney damage if taken with red yeast.
In theory, red yeast may increase the risk of bleeding when taken with drugs that increase the risk of bleeding. Some examples include aspirin, anticoagulants (“blood thinners”) such as warfarin (Coumadin®) or heparin, anti-platelet drugs such as clopidogrel (Plavix®), and non-steroidal anti-inflammatory drugs such as ibuprofen (Motrin®, Advil®) or naproxen (Naprosyn®, Aleve®).
Red yeast may produce gamma-aminobutyric acid (GABA) and therefore can have additive effects when taken with drugs that affect GABA such as neurontin (Gabapentin®).
Red yeast may also interact with digoxin, niacin, thyroid medications, and blood pressure-lowering medications. Caution is advised.
Red yeast may alter blood sugar levels; patients with diabetes or taking insulin or blood sugar-lowering medications by mouth should consult with a qualified healthcare professional, including a pharmacist. Dosing adjustments may be necessary.
Interactions with Herbs and Dietary Supplements
Red yeast may interact with products that cause liver damage or are broken down in the liver. Grapefruit juice may increase blood levels of red yeast. Milk thistle, St. John’s wort, niacin, and vitamin A may interact with red yeast rice extract. Coenzyme Q10 levels may be lowered by red yeast rice extract. Cholesterol-lowering herbs and supplements such as guggul or fish oils may have increased effects when taken with red rice yeast. Although not well studied, red yeast may also interact with astaxanthin and zinc. Caution is advised.
Certain herbs and supplements may interfere with the way the body processes red yeast using the liver’s “cytochrome P450” enzyme system. Inhibitors of cytochrome P450 may increase the chance of muscle and kidney damage if taken with red yeast.
In theory, red yeast may increase the risk of bleeding when taken with herbs and supplements that are believed to increase the risk of bleeding. Multiple cases of bleeding have been reported with the use of Ginkgo biloba , and fewer cases with garlic and saw palmetto. Numerous other agents may theoretically increase the risk of bleeding, although this has not been proven in most cases.
Red yeast may also interact with digitalis (foxglove), or herbs and supplements that affect the thyroid or blood pressure. It may also have anti-inflammatory effects and should be used cautiously with other herbs or supplements that may have anti-inflammatory effects.
Red yeast may alter blood sugar levels in the blood, and patients with diabetes or taking herbs and supplement to control blood sugar should use with caution.
Disclaimer:The information presented herein is intended for educational purposes only. Individual results may vary, and before using any supplements, it is always advisable to consult with your own health care provider.
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