Garlic, a popular culinary herb, has been used as a medical remedy in traditional medicine, for centuries and confirmed for its protective health benefits in current medical science. The intake of fresh garlic, in amounts needed for its health efficacy is accompanied by side effects of unpleasant odor that lingers on the breath and skin and potential gastrointestinal adverse effects of diarrhea and flatulence. Thus, many shun this important herb and are deprived of its benefits.
An important and effective alternative was developed by the Wakunaga Company, originally in Japan and now also as Wakunaga of America, in California. The company manufactures Kyolic® Aged Garlic Extract (AGE™), an odorless supplement that has been shown in over 700 peer reviewed scientific and medical publications to have the health benefits of fresh garlic and often even a higher efficacy, without any of the side effects of the fresh bulb.
While the health benefits of AGE are many, helping protect against cardiovascular disease, neurodegenerative disease, some forms of cancer, and has anti-aging and anti-inflammatory effects, this article will focus on the cardiovascular benefits as proven in research and in the clinic.
Aged Garlic Extract
Aged garlic extract is manufactured from organic fresh garlic, by extraction and aging for 20 months at room temperature. The result is a highly bioavailable odor-free supplement, rich in organosulfur compounds, largely water soluble, such as S-allyl Cysteine and S-allyl meractocysteine (unique to AGE), as well as other substances with antioxidant activity, including oil soluble organosulfur compounds, allixin, selenium, saponins and flavonoids. AGE is a supplement with high quality control, standardized by S-ally cysteine, its key compound.
Risk Factors for Cardiovascular Disease
Risk factors for cardiovascular disease include oxidative stress, elevated LDL cholesterol and triglycerides, low HDL (the good cholesterol), hypertension and high homocysteine; being overweight also increases risk.
High LDL cholesterol promotes inflammation in the arteries, causing further accumulation of cholesterol in the arterial walls; this in turn produces more inflammation. Eventually the deposited cholesterol hardens into a plaque, which can rupture and lead to blood clots that cause heart attacks and strokes.
Reactive oxygen species and oxidant stress are implicated in cardiovascular diseases. Oxidative damage to DNA, proteins, lipids, and other molecules rank highly as a major cause in the onset and development of these diseases. Reactive oxygen species, including free radicals, that are the cause of oxidant stress, in the absence of enough antioxidants, are byproducts of normal metabolism and increase during infection and inflammation, elevated homocysteine and exposure to exogenous sources, including environmental pollutants, smoking, certain drugs (e.g., acetaminophen), and radiation.
AGE and Cardiovascular Disease
AGE, with its antioxidant activities, has been shown to modulate cardiovascular risk factors in both clinical and preclinical settings. AGE has been found to reduce blood pressure, inhibit platelet aggregation and adhesion, lower LDL and elevate HDL cholesterol, reduce smoking-related oxidative damage, inhibit the production of prostaglandins involved in inflammation, and lower homocysteine. S-allyl cysteine has been found to lower cholesterol by deactivating the enzyme involved in cholesterol synthesis (3-hydroxy-3-methylglutaryl-CoA) by as much as 41 percent. AGE efficacy in reducing cholesterol synthesis is additive with statins. Other possible contributors to protection against cardiovascular disease are the effects of AGE in increasing microcirculation and protecting the lining of arteries, (endothelial cells) from oxidative damage, a factor notably important in diabetes, where microvasculature is damaged and the risk of heart disease is high. AGE can also temporarily increase, by 30–40 percent, the synthesis of cellular nitric oxide that helps regulate blood pressure. Major findings have shown that AGE inhibits the progression of coronary-artery calcification, thus reducing the risk of a myocardial infarct.
Calcification and Heart Disease
Calcium deposition in the walls of coronary arteries is an active process. Calcification is an early feature of atherosclerotic plaque formation, beginning with fatty-streak formation and continuing throughout the development of the plaque, resulting in a narrowing of the arteries.
Studies by Dr. Matthew Budoff and colleagues at the University of California (UCLA) have shown repeatedly in a number of placebo-controlled randomized clinical studies, that AGE significantly reduces the progression of plaque formation compared to placebo, as determined by serial coronary artery calcium measurements, as described below. Other findings in patients taking AGE showed improved endothelial function, reduced LDL cholesterol, a lowering of an inflammation marker C reactive protein, and homocysteine and improving HDL cholesterol. The investigators concluded that the study, “helps establish garlic therapy as an anti-atherosclerosis therapy in patients with, and without coronary artery disease.”
The early one year study by the Budoff group on the role of AGE in plaque progression, was a placebo-controlled, double-blind, randomized pilot study to determine if atherosclerotic plaques, detected by electron beam tomography, will progress at a different rate with the intake of AGE, as compared with a placebo. 19 patients (14 men, five women, mean age of 59.9 ± 10.5 y) completed the study. Subjects received either 1200 mg AGE a day or the equivalent amount of placebo. The patients were on statin therapy and aspirin during the study. The blood marker used for compliance was S-allyl cysteine, the major active compounds in AGE, considered the only reliable human compliance marker in studies on garlic consumption.
The results of this yearlong study showed that patients taking AGE had an absolute change in the calcium score, (indicating plaque progression) of 45.2 +/-57.2, while the placebo group was 129.0 ± 102.1, significantly greater than the AGE group. All patients in this study were on statin therapy, meaning that the improvement seen by the intake of AGE was additive to the benefit of statin therapy. Plaque progression was at a rate of 22.2 percent per year in the placebo group, while the intake of AGE reduced progression to 7.5 percent. In the most recent study, presented by Dr. Budoff's group at the American College of Cardiology's 64th annual scientific meeting, in May 2015, the investigators pooled four placebo-controlled, double-blind, randomized studies to examine AGE's effect on blood pressure as well as progression of calcification. The studies involved 161 people, randomized to take, daily, either 1000 mg AGE or placebo, for one year. Blood pressure was checked at the beginning and end of the study. Testing was done to examine coronary artery calcification.
One year later, the UCLA researchers found a reduction in blood pressure in the subjects taking AGE; AGE also inhibited the progression of coronary artery calcification by 1.78 fold, compared with placebo, over the course of the study. The principal investigator, Dr. Matthew Budoff, stated, "these new findings provide cardiologists and internists with an additional tool for patients who are at a high risk of cardiovascular disease. It also gives patients with mild to moderate cardiovascular disease a proactive way to reduce those risk factors."
Elevated homocysteine damages endothelial cells that line blood vessels and induces thrombosis that can lead to heart attacks and stroke. Homocysteine produces breaks in DNA and induces apoptosis, a programmed cell death. Consumption of AGE has been shown to reduce homocysteine levels. In a preclinical study, levels of homocysteine in a 4-week folatedeficient diet containing AGE were compared with a folatefortified diet containing AGE. Plasma homocysteine was 30 percent lower in the folate-deficient models that received AGE, but not in those with adequate folate. The results suggest that AGE may serve as an added treatment in hyperhomocyteinemia. A clinical study, showing that AGE inhibits the progression of coronary artery calcification, also showed a trend in lowering homocysteine levels.
Age And Inflammation
Prostaglandins, play a key role in Inflammation, a risk factor in heart disease as well as other pathological conditions, including neurodegenerative disease and cancer. In a study by Rahman and colleagues the role of AGE in modifying prostaglandins was tested in smokers and non smokers. At the start of the trial, the plasma concentration of prostaglandin 8 iso PGF2ƒ¿ was about 58 percent greater in smokers than in nonsmokers. A 14 days supplementation with AGE resulted in a 35 percent reduction in the plasma prostaglandin in smokers, and a 29 percent reduction in non smokers.
The prostaglandin studied plays a role in cardiovascular disease by increasing the stickiness and adhesion of platelets, thus increasing the risk of plaque formation, constriction of arteries and atherosclerosis; the prostaglandin has been shown to be present in increased amounts in human atherosclerotic vascular tissue compared with healthy tissue. The decrease in 8 iso PGF2ƒ¿ following AGE intake supports earlier findings of AGE decreasing platelet aggregation. This study further confirmed that dietary supplementation with AGE with its powerful antioxidant capabilities, can protect against heart atherosclerosis and heart disease, which are associated with increased oxidative stress and inflammation.
Kyolico Aged Garlic Extract (AGE), a natural odorless supplement produced from organically grown fresh garlic, by Wakunaga of America has a wide range of health effects including the ability to lower the risk of heart disease. AGE has been shown in clinical studies to reduce atherosclerotic plaque formation, lower LDL cholesterol and triglycerides, decrease hypertension, prevent platelet aggregation, lower levels of homocysteine, and other inflammatory factors, including a critical prostaglandin. AGE taken daily can help reduce the risk of heart disease that is a major cause of death in our society.
- Varshney R, Budoff MJ. Garlic and Heart Disease. J Nutr. 2016 Jan 13. pii: jn202333. [Epub ahead of print] Review.
- Budoff M. Aged garlic extract retards progression of coronary artery calcification. J Nutr. 2006 Mar;136:741S.4S.
- Allison GL, Lowe GM, Rahman K. Aged garlic extract inhibits platelet activation by increasing intracellular cAMP and reducing the interaction of GPIIb/IIIa receptor with fibrinogen. Life Sci. 2012 Dec 17;91(25.26):1275.80. doi:10.1016/j.lfs.2012.09.019. Epub 2012 Oct 13.
- Dllon SA, Lowe GM, Billington D, Rahman K. Dietary supplementation with aged garlic extract reduces plasma and urine concentrations of 8-iso-prostaglandin F(2 alpha) in smoking and nonsmoking men and women. J Nutr. 2002 Feb;132:168.71.
- Ide N, Keller C, Weiss N. Aged garlic extract inhibits homocysteine-induced CD36 expression and foam cell formation in human macrophages. J Nutr. 2006 Mar;136:755S.8S
- Borek C. Garlic reduces dementia and heart-disease risk. J Nutr. 2006 Mar;136: 810S.812S.