by CJ Puotinen
Updated Information from NEHA Journal Winter, 2003 Issue
That attitude may soon change, for the latest herb to be recognized for its cancer-fighting properties was discovered not by alternative practitioners but by medical researchers working at a respected university.
The herb is sweet Annie (Artemisia annua), also known in the West as sweet wormwood or annual wormwood and in China as Qinghao. Its cousin is the more familiar perennial wormwood, Artemisia absinthium.
The discovery’s story began during the Vietnam War, when the North Vietnamese army constructed an elaborate network of underground tunnels. As the tunnels collected rainwater, mosquitoes that carried malaria reproduced in their standing water. The problem grew so severe that North Vietnam lost more soldiers to malaria than to military weapons.
Ho Chi Min, North Vietnam’s leader, turned to China for help, and Chairman Mao Tse-tung assured him that China’s scientists could develop a new malaria cure. Researchers at the Chinese Institute of Material Medicine found a region of China that reported no malaria cases, and when they investigated, they discovered that its people drank a decoction (simmered tea) of Artemesia annua at the first sign of malarial symptoms.
In 1972, the scientists isolated four chemical compounds in the plant: artesunate, artemether, arteether, and artemisinin. Three have medicinal applications.
Artesunate, which is a water-soluble synthetic compound, is the most active and least toxic of the four, but it breaks down rapidly in the body.
Artemether, another synthetic compound, is fat-soluble, breaks down slowly, and is the most toxic of the four when taken in high doses. Its therapeutic dose is far below the danger level. Artemether’s main advantage is that it can cross the blood-brain barrier.
Artemisinin, which occurs naturally in sweet wormwood, is the least expensive compound to produce, and it’s considered the safest and most effective. It, too, crosses the blood-brain barrier. Some practitioners use artemisinin alone, while others prefer combinations of artemisinin and artesunate and/or artemether.
Artemisinin became the drug of choice for malaria. It has since become popular throughout Southeast Asia and Africa, where malaria has become resistant to nearly all anti-malarial drugs, including chloroquine, quinine, mefloquine, and Fansidar. Malaria infects an estimated 270 million people worldwide, with about 80 percent of cases occurring in Africa. So far, malaria has not developed resistance to artemisinin.
In 1993, a University of Michigan researcher discovered the biochemical mechanism that makes artemisinin work. Dr. Steven R. Meshnick, a parasitologist at the University’s School of Public Health, found that the malaria parasite survives in its host by consuming approximately 25 percent of the hemoglobin in the host’s red blood cells. However, it does not metabolize the heme (iron) in the hemoglobin. Instead, it stores the iron in the form of a polymer called hemozoin, inside a food vacuole.
“We discovered that when artemisinin comes into contact with the iron in the hemozoin,” he said, “the iron converts the drug into a toxic chemical, releasing a free radical that destroys the parasite.” In Dr. Meshnick’s clinical study of 638 malarial patients in Vietnam, artemisinin eliminated 98 percent of malarial parasites within 24 hours and did so without significant side effects. “The parasite reappeared in only 10 to 23 percent of the group that took artemisinin for five to ten days,” he said. “It may well be that the re-appearance of the disease was due to a new infection rather than a flare-up of the prior one.” Artemisinin was equally effective against both the falciparum and vivax strains of malaria.
Artemisinin’s reaction to iron molecules interested Research Professors Henry Lai, Ph.D., and Narendra Singh, M.B.B.S., at the University of Washington in Seattle because cancer cells, like malaria parasites, collect and store iron. “Cancer cells need extra iron to replicate DNA when they divide,” explains Professor Lai. “As a result, cancer cells have a much higher concentration of iron than normal cells do. When we began to understand how artemisinin works, I wondered if we could use that knowledge to target cancer cells.”
In research published in 1995 in the journal Cancer Letters and in the November 2001 journal Life Sciences, Professors Lai and Singh found that artemisinin killed all of the human leukemia and breast cancer cells in a test tube within 8 to16 hours while leaving nearly all of the normal cells unharmed.
Artemisinin has been shown in test tube studies to be most effective against leukemia and colon cancer, while preliminary tests suggest that artemisinin will be effective against melanoma, breast, ovarian, prostate, renal, and central nervous system cancers such as glioblastoma and neuroblastoma.
In 1999, Professors Lai and Singh pioneered canine research on artemisinin when, in collaboration with Tejinder Sodhi, DVM, of the Animal Hospital of Lynnwood in Lynnwood, Washington, they treated a male Golden Retriever whose bone tumor caused acute lameness. Despite a very low dose and short treatment time (artemisinin was then expensive and the project lacked funding to buy more), the dog recovered after 10 days of treatment, gaining weight and walking normally, with x-rays showing signs of bone remodeling. In another case, a 7-year-old male Basset Hound was diagnosed with lymphosarcoma of the lymph nodes. After three 5-day treatments separated by intervals of three to five days, the diameter of inguinal and submandibular, right and left, lymph nodes were reduced to half. Both dogs recovered without further treatment.
As this article goes to press (April 2003), the Washington Cancer Institute Department of Orthopedic Oncology, Georgetown University Medical Center, and a fellowship-trained veterinary surgical oncologist in Washington, DC, are collaborating on a project to determine whether artemisinin is an effective compound in the treatment of canine osteosarcoma. “We are performing in vitro or laboratory assays, the results of which will be determined by June 2003,” says Senior Clinical Researcher Kristen Kellar-Graney at the Washington Cancer Institute. “If these results prove favorable, it is our intention to perform a small, double-blinded, randomized study with pet canines who are not eligible for other forms of conventional treatment or pets whose owners are not interested in or cannot afford more conventional methods of treatment.”
Sweet Annie grows around the world, but not every plant contains artemisinin. The most productive plants have been found on plantations in North Vietnam near Hanoi and in the wild on steep hills in China’s Chongqing province, especially at altitudes above 1000 meters (3000 feet). Holley Pharmaceuticals imports high-quality artemisinin from China. According to Holley USA’s president Michael Liu, the leaves of Artemisia annua are harvested just before budding, sun-dried for a day, then transported in specially designed trucks to a nearby factory. “They are first extracted by a fat solvent,” he explains, “then the base liquid is separated. A second extraction is done with an organic solvent, then the extract is concentrated and crystallized, producing crude artemisinin. The dissolution, filtration, concentration, and recrystallization steps are repeated several times until the result is pure artemisinin, which is tested by high performance liquid chromatography (HPLC) for purity and tested against cancer cell lines for bio-assay.”
The recommended human dose is approximately 1 milligram (mg) of artemisinin per kilogram (2.2 pounds) of body weight twice per day. For a 100-lb person, this would be 45 mg twice a day, and for someone weighing 180 lbs, it would be 82 mg twice a day. Because artemisinin is sold in 50-mg and 100-mg capsules, these doses are usually rounded up to the closest available dose. According to the researchers interviewed here, artemisinin should be taken for at least one month and can be taken for up to six to twelve months at a time.
Vitamin C, coenzyme Q10, pancreatic enzymes, medicinal herbs, and other supplements used in holistic cancer therapies are compatible with artemisinin, although some practitioners recommend separating artemisinin and high doses of vitamin C by at least three hours.
Some practitioners recommend giving cod liver oil or other fat with artemisinin to improve its assimilation, but Professor Lai reports that this is not necessary.
Artemisinin should not be combined with radiation therapy because radiation treatments release iron stored in cancer cells to surrounding tissue. For best results, patients are encouraged to wait until at least two months after their last radiation treatment before beginning artemisinin.
However, artemisinin is compatible with chemotherapy. In a study published in 2002, German researcher T. Efferth, Ph.D., tested artemisinin in combination with 22 chemotherapy drugs and found that artemisinin enhanced the drugs’ effectiveness. When artemisinin is used in combination with chemotherapy, it should be taken several hours after the chemotherapy treatment ends. When taken in combination with chemotherapy, artemisinin does not alleviate chemotherapy’s side effects.
In the May 2002 issue of his Second Opinion newsletter (PO Box 467939, Atlanta GA 31146-7939, phone 1-800-728-2288 or 770-399-5617), Robert J. Rowen, MD, reported on several cases in which he and other physicians used artemisinin with excellent results. Dr. Rowen reprinted these in his booklet “New Breakthroughs for Preventing and Surviving Cancer,” available from the same publisher. In one case, he treated a 47-year-old mechanic with a tumor on his head just after the man’s oncologist diagnosed lymphoma. Dr. Rowen immediately prescribed artemisinin, which the patient took for two weeks. At the end of that time, the lump developed a small depression in its center, but the perimeter had grown slightly. The patient felt discouraged and decided not to continue taking artemisinin. He received no other medical treatment. Four weeks later, his tumor disappeared.
Dr. Rowen has also interviewed Vietnamese physicians have used artemisinin for ten years. They report a long-term remission success rate of 50 to 60 percent in 400 cancer patients treated with artemisinin combined with a comprehensive integrative cancer strategy. See Dr. Rowen’s publications for further information.
In addition to curing malaria and some cancers, artemisinin may have other applications.
Like several members of the Artemisia family, sweet wormwood has been used in herbal products that treat internal parasites. Although this use is experimental, some practitioners recommend artemisinin as an anti-parasite therapy.
While all agree that cancer is best treated in its earliest stages, no one has formally tested artemisinin as a cancer preventive or determined whether it is safe for use by those who don’t have cancer or who might or might not have undiagnosed, early-stage cancer. Some health care practitioners are experimenting with one-month courses of artemisinin for themselves or their pets. Also, some physicians have reported good results from treating Lyme disease with artemisinin. These are experimental or untested applications of the product. No doubt they will be explored by researchers in the future.
As exciting and convenient as this new product is, some herbalists prefer to use the whole herb or whole-herb extracts rather than the “silver bullet” of refined artemisinin. One is botanist James A. Duke, Ph.D., prolific author, researcher, expert on the medicinal benefits of herbs and, until his retirement, affiliated with the U.S. Department of Agriculture.
“Sweet Annie contains half a dozen or more antiviral compounds,” he explains, “some of which are proven synergic. One naturopathic physician, Dr. S. Morris, was on ecotour in NgoraNgora Crater, where all mosquitoes are malarial. He took a tincture of Artemisia annua instead of chloroquine or larium, which the rest of us were taking for malaria prevention. None of us go malaria. Subsequently, that’s what I have taken as a preventive in Amazonian Peru, where even my shaman caught malaria.”
According to Dr. Duke, some research has shown that the whole herb is more active than artemisinin, that gelatin capsules of the herb are 3.5 times more effective than artemisinin for clearing parasitemia in mice. “The whole-herb capsules are better than chloroquine for fever and malarial symptoms,” he says. “When it comes to malaria, I personally believe that whole extracts of Artemisia annua, with all their synergens, could be better and cheaper than the isolated silver bullet, or derivatives thereof, at preventing as well as treating malaria. It could have fewer side effects and would be less likely to lead to multidrug resistance.
“But when it comes to cancer, there are few cut and dried answers. I would myself experiment with tinctures, cold-water infusions, and hot teas of Artemisia annua for a recalcitrant cancer. This is not a recommendation for anyone, it’s just my personal opinion. Perhaps the answer will be found by testing whole-herb cold-water extracts in human beings.”
Holley Pharmaceuticals artemether (40-mg softgels and tablets), artesunate (50-mg capsules), and other products derived from artemisinin are available only to healthcare professionals, research scientists, or customers living outside the United States. For information on these products, contact firstname.lastname@example.org.
Allergy Research Group in Hayward, CA (phone 1-800-545-9960, www.allergyresearchgroup.com) offers three supplements derived from Sweet Annie that are sold in health food stores. Artemisia capsules contain 500 mg powdered Artemisia annua ; Artemisia Forte II capsules contain 150 mg Artemisia annua, 10 mg artemisinin, and 125 mg citrus seed extract ; and artemisinin capsules contain 100 mg artemisinin.
For information regarding cancer research and treatment using artemisinin, contact Professor Henry Lai, Ph.D., University of Washington, Seattle. Phone 206-543-1071, email email@example.com.
For information regarding canine cancer research using artemisinin, contact Kristen Kellar-Graney, Washington Cancer Institute, Washington, DC. Phone 202-877-3390, www.sarcoma.org, email firstname.lastname@example.org.