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June 11, 2010
Green tea compound shows promise in chronic lymphocytic leukemia
Readers of Life Extension Update may recall the May 29, 2009 issue which revealed the results of a Phase I clinical trial reported in the Journal of Clinical Oncology which tested the effects of an extract of green tea in patients with chronic lymphocytic leukemia (CLL). Now, at the annual meeting of the American Society of Clinical Oncology (ASCO) held this month in Chicago, researchers from the Mayo Clinic report results from a Phase II trial which provide additional evidence of clinical activity and low toxicity for epigallocatechin gallate (EGCG, extracted from green tea) in CLL patients.
Chronic lymphocytic leukemia, a hybrid between lymphoma and leukemia, is currently not treated until it shows signs of progression, which is determined by the quantity of leukemic cells in blood and bone marrow. The Mayo Clinic's work with EGCG in CLL began 8 years ago with promising experiments involving cultured cells, in which the compound reduced leukemic cell survival. In the latest investigation, hematologist Tait Shanafelt, MD and colleagues gave the highest dose of EGCG tested in the Phase I trial (2,000 milligrams) to 36 new patients with early stage, asymptomatic CLL. The extract was administered twice per day for up to 6 months.
Among 41 subjects who completed 6 months of high dose EGCG (including 6 from the phase I trial), 31 percent experienced a 20 percent or greater reduction in blood leukemia count, and 69 percent of those with lymph node enlargement had their node size reduced by at least half. The majority of side effects that occurred in association with EGCG were low grade and transient.
“Although only a comparative phase III trial can determine whether EGCG can delay progression of CLL, the benefits we have seen in most CLL patients who use the chemical suggest that it has modest clinical activity and may be useful for stabilizing this form of leukemia, potentially slowing it down," Dr Shanafelt commented. “All in all, the treatment was well tolerated with very mild side effects in most patients.”
“Using nontoxic chemicals to push back cancer growth to delay the need for toxic therapies is a worthy goal in oncology research — particularly for forms of cancer initially managed by observation such as CLL,” added coauthor Neil Kay, MD, whose laboratory first tested green tea extract in human CLL cells. "Without a phase III clinical trial, we cannot make a recommendation that EGCG be used by CLL patients, but those who want to take supplements should consult with their oncologists and need to receive appropriate monitoring using laboratory tests."
Leukemia refers to cancers that begin in the blood-forming cells of the body. These abnormal cells grow and multiply in an uncontrolled way. As the disease progresses, leukemic cells move through the bloodstream and invade other organs, such as the spleen, lymph nodes, liver, and central nervous system. In the US, more than 30,000 new cases of leukemia are diagnosed every year, and adult onset accounts for 90 percent of the new cases (Xie Y et al 2003).
Leukemia can be classified into four major types based on whether the disease is acute or chronic and according to the type of white blood cell affected:
- Acute myelogenous leukemia (AML)
- Chronic myelogenous leukemia (CML)
- Acute lymphocytic leukemia (ALL)
- Chronic lymphocytic leukemia (CLL)
An extract of the spice turmeric, curcumin acts in combination with the soy isoflavone genistein to reduce the number of leukemia-promoting properties, such as growth signals and pro-inflammatory cytokines that are over-produced in leukemia (Arbiser JL et al 1998). Curcumin has been shown to:
- Inhibit production of bFGF, a potent growth signal for cancer cells that is known to be over-produced in AML, CML, and ALL (Arbiser JL et al 1998).
- Increase expression of the cancer-protective p53 gene in leukemia cell lines, thus making them more susceptible to cell death (Jee SH et al 1998).
- Reduce the production of the inflammatory cytokine, TNF-alpha, that is over-produced in CML and ALL (Xu YX et al 1997).
Epigallocatechin gallate (EGCG) in green tea blocks the production of vascular endothelial growth factor (VEGF), considered essential for leukemia growth and spread (Lee YK et al 2004). EGCG may be particularly useful in CLL, a leukemia type that relies heavily on VEGF for its survival. EGCG significantly increased the rate of cell death in 8 out of 10 CLL samples (Lee YK et al 2004). Green tea blocks the proliferation of lymphocytes from adult T cell leukemia patients (Li HC et al 2000). Theaflavins found in black tea have also been shown to be as potent as EGCG from green tea in blocking proliferation of leukemia cell lines (Lung HL et al 2004).
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SAMe (S-adenosyl-methionine) is an amino acid derivative normally synthesized in the body. SAMe is used by the body in three important pathways:
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