Garlic and Cancer and Cardiovasular Disease

Effect of aged garlic extract (AGE) has been tested in the placebo-controlled double blind randomized clinical study that determined that the atherosclerotic plaque burden detected by electron beam tomography (EBT) changed significantly with the use of aged garlic extract, Patients in Dr. Budoff’s study were able to significantly lower their total cholesterol, blood pressure, homocysteine and LDL cholesterol oxidation levels with aged garlic extract supplementation.

“Garlic is turning out to be a major player in cancer and heart disease prevention and control, especially in combination with drug treatments,” said Richard Rivlin, M.D. of Strang Cancer Prevention Center at Cornell. “It’s also showing us that we can start early. It’s madness to treat cancer and heart disease in their advanced stages. We need to start early and aged garlic extract is an excellent way to do that.”

Almost 400 scientific studies have been completed on aged garlic extract, done in major universities worldwide. These studies have focused on a variety of heart disease risk factors such as cholesterol, high blood pressure, homocysteine levels, inhibiting LDL oxidation, anti-platelet aggregation and adhesion, stimulating blood circulation; in addition to other studies on immune stimulation, cognitive effects, liver function and anti-tumor effects. .

Abstracts

PRECLINICAL PERSPECTIVE ON GARLIC AND CANCER. John A. Milner, National Cancer Institute, Rockville, MD 20892

Mounting evidence points to the anticancer properties of fresh garlic extracts, aged garlic, garlic oil, and a number of specific organosulfur compounds from garlic. These prevention characteristics arise through both a dose and temporal related change in several cellular events including those involving drug metabolism, immunocompetence, cell cycle regulation, apoptosis and angiogenesis. A block in carcinogen activation through modulation of cytochrome P450-dependent monooxygenases and/or acceleration of carcinogen detoxification via induction of phase II enzymes likely account for some of this protection. The block in preneoplastic lesions and/or tumors in several sites suggests a generalizable mechanism. The efficacy of water- and lipid-soluble allyl sulfur compounds against chemical carcinogenesis appears comparable, although more studies are needed. A shift in sulfhydryl groups, redox status or enzyme catalysis may account for some of the phenotypic changes. They may also account for the observed hyperphosphorylation of specific cell cycle related proteins and histone hyperacetylation; both of which have been correlated with suppressed tumor cell proliferation. Several forms of allyl sulfur compounds are effective in blocking cell division and inducing apoptosis, but notable differences in the efficacy among these various compounds and across tumor types are evident. While the expression of many genes and proteins can be influenced by allyl sulfides; the challenge is to determine which is responsible for a phenotypic change. Additional studies are needed with more modest exposures and over prolonged periods and that utilize transgenic and knockout models to assist in the identification of molecular targets. Finally, additional research is needed to identify sensitive “effect” and “susceptibility” biomarkers that can ultimately be used to identify responders from non-responders.

INHIBITION OF CORONARY ARTERIAL PLAQUE ACCUMULATION BY GARLIC. Matthew Budoff, Harbor-UCLA Medical Center, UCLA School of Medicine, California, USA

Effect of Aged garlic extract (AGE) has been tested in the placebo-controlled double blind randomized clinical study to determine whether the atherosclerotic plaque burden detected by electron beam tomography (EBT) will change at a different rate under the influence of AGE or placebo. EBT can non-invasively quantitate the amount of coronary calcification and track atherosclerotic plaque over time. Nineteen of 23 patients completed the study protocol. The patients were well matched for age, gender, statin use and cardiac risk factors. Patients underwent EBT and blood testing at baseline, and then again after 12 months of randomization. The average change in the calcium score (Volumetric method) ± SD for the AGE group (n = 9) was 7.5 ± 9.4% over the one year. The placebo group (n = 10) demonstrated 22.2 ± 18.5% annual progression, significantly greater than the treated cohort (p = 0.01). While there were no significant changes in cholesterol parameters, or C Reactive protein between the groups, high density lipoproteins and plasma homocysteine in the AGE group demonstrated a trend toward improvement compared to the placebo patients. Thus, although this is a small-scale trial, it demonstrates the potential of AGE to inhibit the rate of atherosclerosis (progression of coronary calcium), as compared to placebo over one year. Larger studies need to be performed to assess this potential anti-atherosclerotic therapy and the impact on coronary events.

INFLUENCE OF GARLIC ON ENDOTHELIAL DYSFUNCTION IN HYPERHOMOCYSTEINEMIA. N. Weiss, N. Ide, T. Abahji, L. Nill, C. Keller, U. Hoffmann. Klinikum der Universität München, D-80336 Munich, Germany

Endothelial dysfunction (ED) due to decreased bioavailable nitric oxide (NO) by increased vascular oxidant stress plays a critical role in the vascular pathobiology of hyperhomocysteinemia (hhcy). Aged Garlic Extract (AGE) minimizes intracellular oxidant stress and stimulates NO generation in endothelial cells. We performed a placebo-controlled, blinded, cross-over study to examine whether AGE prevents macro- and microvascular ED during acute hhcy induced by an oral methionine challenge in healthy subjects. Acute hhcy leads to a significant decrease in flow-mediated vasodilation of the brachial artery as determined by vascular ultrasound, indicative of macrovascular ED, as well as a decreased number of recruited nailfold capillaries during postischemic reactive hyperemia as determined by videomicroscopy, and to a decreased ratio of acetylcholine (endothelium-dependent) vs. sodium nitroprusside (endothelium-independent) iontophoresis induced skin perfusion as measured by laser doppler flowmetry, indicative of microvascular ED. Preliminary results show that pretreatment with AGE for six weeks diminishes the adverse effects of acute hhcy on endothelium-dependent brachial artery vasodilation and on acetylcholine-induced stimulation of skin perfusion. Whether or not this is accompanied by changes in biochemical parameters of ED is still under investigation. It is concluded that AGE may at least partly prevent a decrease in bioavailable NO during acute hhcy.

Bibliographies

David Heber, MD, PhD, FACP, FACN

Professor, UCLA Department of Medicine - Division of Clinical Nutrition, at the David Geffen School of Medicine, UCLA, and UCLA School of Public Health; Director, UCLA Center for Human Nutrition; Director, NIH Center for Dietary Supplement Research in Botanicals (CDSRB); Director, NCI-funded Clinical Nutrition Research Unit; Vice Chair, UCLA Collaborative Centers for Integrative Medicine; Member, UCLA's Jonsson Comprehensive Cancer Center

Matthew Budoff, MD, FACC

Matthew Budoff, MD, FACC, is an associate professor of medicine at the UCLA School of Medicine and program director for the Division of Cardiology, as well as director of the Electron Beam CT Laboratory at Harbor-UCLA Medical Center in Torrance, Calif. He completed his undergraduate work at University of California, Riverside, and earned his medical degree at George Washington University in Washington D.C. Dr. Budoff’s efforts to identify and modify risk factors for cardiovascular disease using electron beam CT have been extensively published. His latest research focuses on the progression of arteriosclerosis.

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