Kyolic Aged Garlic Extract - Monograph

MONOGRAPH

What is Kyolic速 Aged Garlic ExtractTM ?

Indications - Efficacies Clinical Research Summary Mechanisms of Action Contraindications Drug Interactions Side Effects Recommended Dose

F O R

H E A L T H

P R O F E S S I O N A L

U S E

O N L Y

Scientifically Proven Odourless Organic Garlic Supplement

Mechanisms of Action EFFECTS

MECHANISMS

Inhibition of Plaque Formation in the Coronary Artery

Improving vessel function via antioxidant properties and inhibiting scavenger receptor expression, foam cell formation and smooth muscle cell proliferation associated with plaque formation.

Improvement of Endothelial Function in Macro - and Microcirculation

Maintaining blood pressure and blood flow through antioxidant properties. Antioxidant properties include: directly scavenging reactive oxygen species (ROS), modulating NF-kB signal pathway and glutathione redox cycle resulting in enhancing antioxidant enzymes, intracellular antioxidant activity; glutathione, and good nitric oxide (NO) production, and inhibiting the increase in risk factors such as cholesterol and homocysteine.

Modulating Blood Pressure

Maintaining healthy vessel function through antioxidant properties such as protecting endothelial cells from oxidative injury and enhancing good NO production, thus relaxing vessels.

Alpha-antagonistic effect.

Boosting HDL

Decreasing LDL cholesterol while increasing HDL serum levels.

Cholesterol Lowering

Inhibiting HMG-CoA reductase (enzyme to form cholesterol).

Inhibiting absorption of cholesterol from gastrointestinal tract.

Inhibition of LDL-cholesterol Oxidation

Antioxidant properties such as metal chelating, directly scavenging reactive oxygen species and inhibiting lipid peroxidation.

Inhibition of Platelet Aggregation

Competes with agonists, such as adenosine diphosphate (ADP), collagen etc. which are inducers of platelet aggregation. Metal chelating, suppressing calcium mobilization.

Impact on sickle cells

Antioxidant properties.

Reduces Heinz body, which crystallizes red blood cells.

Helps Prevent the Common Cold

Enhances the immune system such as natural killer cells, macrophages, phagocytes, T-Cells, increases antibody production, and lymphocyte functions

Recovery from Cold with General Fatigue (Loss of Energy)

Enhances the immune system.

Stimulates various metabolism systems including assorted enzymes

Scientifically Proven Organic Odourless Natural and Standardized with SAC Quality Control under ISO 9001 & GMP Multiple Health Benefits Scientific Support (500+ papers)

Health Canada – Natural Health Products Directorate – NPN # 80003106 Promotes Heart Health through Cholesterol Reduction when used in combination with dietary measures.

What is Kyolic® Aged Garlic Extract™ ?

It is the superior source of garlic and the proprietary aging process that makes Kyolic® truly unique. Kyolic® Aged Garlic ExtractTM is the only truly odourless garlic supplement available on the Canadian market. The fresh garlic is grown on carefully selected farms under strictly controlled organic conditions without the use of chemical fertilizers, herbicides or pesticides. The crops are cultivated using time-tested procedures to enhance and optimize garlic’s beneficial constituents.

Only the finest garlic is used for the production of Kyolic®.

At harvest, only garlic that meets or surpasses Kyolic®’s demanding standards, is utilized in the proprietary aging process.

First, the garlic cloves are cleaned, sliced and then, under carefully controlled conditions, the sliced garlic is stored in an aqueous ethanol solution in stainless steel tanks where it is naturally aged, without heating, for up to 20 months. Through this unique process, the harsh and unstable organosulfur compounds are converted into mild and effective compounds including the sulfur-containing amino acids (e.g. S-allylcysteine, S-allylmercaptocysteine), and Maillard reaction products that are responsible for Kyolic®’s health benefits. This conversion eliminates odour-causing components, resulting in the truly odourless Kyolic® Aged Garlic ExtractTM comprised of safe, stable, bioavailable and beneficial compounds.

Kyolic® Aged Garlic ExtractTM is manufactured and quality controlled under International Standard Organization (ISO) 9001 and Good Manufacturing Practice (GMP). Aged Garlic ExtractTM also complies with the specifications established by Health Canada and in the US Pharmacopeia / National Formulary (USP/NF) monograph. Aged Garlic ExtractTM, and its various constituents, have been the subject of almost 580 peer - reviewed scientific studies world - wide including Japan, the United States and Europe since its development in 1955.

Indications - Efficacies Kyolic® Aged Garlic ExtractTM supports overall heart health, normal cholesterol levels, circulation and healthy immune function.

Clinical Research Summary STUDY

DESCRIPTION

DESIGN

DURATION

DOSAGE

MEASUREMENT AND RESULTS

Inhibition of Plaque Formation in the Coronary Artery

Budoff, M.; 2006. J. Nutr.

136 Suppl 3: S741-4.

Double Blind Placebo Controlled Trial; n=19 (AGE n=9; Placebo n=10)

1 year

4 mL/day or equiv.

1.2g / day

Calcium scores for the formation of plaque in patients treated with statin medications were evaluated using electron beam computed tomography (EBCT). Approximately 67% of significant reduction in plaque formation was observed in the Kyolic group compared to the placebo group (AGE: 7.5 ± 9.4% vs Placebo: 22.2 ± 18.5%). Blood homocysteine and LDL tended to be reduced, and HDL tended to increase. The data indicates that Kyolic, AGE may be very beneficial and useful for prevention of stopping blood flow to the heart, especially in high-risk people including heart surgery patients.

Improvement of Endothelial Function in Macro- and Microcirculation

Weiss N, Ide N, Abahji T, Nill L, Keller C, Hoffman U.; 2006. J. Nutr. 136 Suppl 3: S750-4.

Double Blind Placebo Controlled Crossover Trial; n=22; (AGE n=11; placebo n=11)

6 weeks

4 mL/day or equiv.

1.2g / day

Flow mediated vasodilation of the brachial artery using vascular ultrasound in macro- and skin perfusion by laser-doppler flowmetry in micro-circulation were used in healthy volunteers. Acute hyperhomocysteinemia led to a significant decrease in both micro- and macro-endothelial function, but pretreatment with AGE significantly diminished the adverse effects of acute hyperhomocysteinemia in both vascular territories (p<0.005). AGE may at least partly prevent a decrease in bioavailable nitric oxide and endothelium-derived hyperpolarizing factor during acute hyperhomocysteinemia. AGE may maintain healthy arteries through reduction of multiple cardiovascular risk factors.

Improvement of Endothelial Function in Macrocirculation

Williams, M.J.A., et al.; 2005. Phytother. Res. 19: 314-9.

Placebo Controlled Crossover Trial; n=30 (AGE n=15; placebo n=15)

2 weeks

2.4 g/day

AGE given to men, with angiographically proven coronary artery disease (CAD) treated with aspirin and statins, demonstrated brachial artery flow mediated endothelium-dependent dilation (FMD) significantly increased (44%, p=0.04). With AGE treatment, FMD levels were significantly higher (p=0.03) as compared to placebo.

This study has shown that AGE may help improve endothelial function in men with CAD..

Improvement of Peripheral Blood Circulation

Mizuno, I., et al., 2005. Oyo Yakuri/Pharmacometrics.

67:371-378.

Open Trial; n=84 (men n=58; women n=26)

4 weeks

2 mL/day or equiv.

0.6g / day

Peripheral blood circulation index was determined using BC-Checker, and ASTRIM SU for width of small veins. AGE with other herbs improved peripheral blood circulation index and the width of small veins. The combination product improves the condition of the peripheral blood circulation, suggesting it may prevent problems such as a stiff shoulder or lower back pain caused by poor peripheral blood circulation. This promising data warrants further investigations.

Improvement of Peripheral Blood Circulation

Kikuchi, N., et al. 1994.

Shinyaku To Rinsho (Jpn. J. New Remedies Clin.) 43(1): 146-158

Placebo Controlled Trial; n=15 (AGE with herb n=10; AGE n=5; control n=5)

4 weeks

1.6 or 2 mL/day or equiv. 0.480g - 0.6g / day

Via skin temperature thermography (colored photographs reflecting temperature of body), AGE with other herbs enhanced microcirculation better than cooked garlic juice in patients who had microcirculation problem.

Various symptoms associated with insufficient microcirculation (headaches, dizziness, vertigo, weariness, lumbago, etc.) were also improved. This promising data warrants further investigations.

Improvement of Peripheral Blood Circulation

Okuhara, T. 1994. Jpn. Pharmacol. Therapeut.

22(8): 3695-3701.

Placebo Controlled Crossover Trial; n=12 (AGE n=6; placebo n=6)

Single administration or 2 weeks

1.6 mL/day or equiv. 0.480g

Using skin thermography, both single administration and continuous administration for 14 days, demonstrated greater improvement of blood flow in subjects receiving liquid AGE as compared to those receiving heated garlic juice. This promising data warrants further investigations.

Boosting HDL

Macan, H., et al., 2006. J. Nutr. 136: 793S-795S.

Double Blind Placebo Controlled Randomized Trial; n=48 (AGE n=22; placebo n=26)

12 weeks

10 mL/day or equiv.

3.0g/day

Patients treated with warfarin receiving AGE (5 mL twice daily) for 12 weeks demonstrated significant increase (3%) in HDL as compared to placebo (P=0.038; n=52). This data indicates AGE supplementation can boost HDL levels. This promising data warrants further investigations.

Cholesterol Lowering

Yeh, Y., et al.; 1997. In Food Factors for Cancer Prevention. Ohigashi, et al.; eds., p226-230. SpringerVerlag, Tokyo.

Double Blind Randomized Placebo Controlled Trial; n=34 (AGE n=17; placebo n=17)

5 months

7.2 g/day

The cholesterol-lowering properties of AGE were determined in hypercholesterolemic men (241±21 mg/dL).

AGE supplementation was found to reduce total cholesterol and LDL-cholesterol by 7% and 10%, respectively (p<0.05). The data indicate that daily supplementation of AGE for 5 months without diet modifications has a mild (but significant) cholesterol-lowering effecting in hyper-cholesterolemic men.

Budoff, M., Takasu, J. et al.; 2004. Prev. Med. 39(5): 985-91.

Yeh, Y., et al. ; 1995. J. Am. Coll. Nutr. 13:545 Cholesterol Lowering

Kawashima, Y., et al.; 1989.

Shinryou To Shinyaku (Treat.

New Med.) 26: 377-388.

Open Trial; n=19 (men n=9; women n=10)

16 weeks

4 mL/day or equiv.

1.2g / day

The changes of lipids by AGE preparation containing vitamin B1, vitamin B12 and liver extract were examined in hyperlipemic patients. Significant reductions in serum cholesterol (234±10 mg/dL 213±10 mg/dL) by 9%, triglycerides (229±20 mg/dL 190±16 mg/dL) by 17% and LDL cholesterol (152±10 mg/dL 138±10 mg/dL) by 9% were observed.

Cholesterol Lowering

Lau, BHS., et al.; 1987. Nutr.

Res. 7: 139-149.

Placebo Controlled Trial; AGE n=25

6 months

4 mL/day or equiv.

1.2g / day

Effect of AGE on plasma cholesterol in subjects (220-440 mg/dL) was compared with placebo. Cholesterol levels in the AGE group significantly dropped (12-31%) as compared to the placebo group. LDL and triglyceride levels were also significantly reduced with AGE (p<0.05). HDL cholesterol was increased in AGE group (p<0.05).

Cholesterol Lowering

Steiner, M., et al. 1996.

Shinyaku To Rinsho (New Drug Clin.) 45(3): 456-466.

Steiner, M. and Lin, R. 1996. Am. J. Clin. Nutr. 64: 866-870.

Double Blind Placebo Controlled Trial; n=82 (AGE n=41; placebo n=41)

6 months

7.2 g/day

AGE reduced LDL cholesterol (8%: p=0.0001) in free-living men with high cholesterol levels (220-290 mg/dL) on a low fat/low cholesterol diet. Triglycerides were significantly reduced 18.9% compared to baseline and 6.7% compared to placebo. AGE significantly reduced platelet adhesion to fibrinogen 34-58% and 10-25% in platelet aggregation (platelets sticking together and clumping). Compared to baseline, significant reductions in both systolic and diastolic blood pressure (9% decrease, respectively) were noted. AGE has beneficial effects on the lipid profile and blood pressure of moderately hypercholesterolemic subjects.

Inhibition of Platelet Aggregation

Rahman K. and Billington, D. 2000. J. Nutr. 130: 2662-2665.

Open Trial; n=23 (men n=12; women n=11)

13 weeks

5 mL/day or equiv.

1.5g / day

In human subjects with normal cholesterol level, AGE significantly inhibited both the total percentage and initial rate of platelet aggregation induced by adenosine diphosphate (ADP). AGE may be beneficial in protecting against cardiovascular disease as a result of inhibiting platelet aggregation.

Inhibition of Platelet Aggregation

Steiner, M. and Lin, R. 1998. J. Cardiovascular Pharmacol. 31: 904-908.

Double Blind Placebo Controlled Trial; n=30 (AGE n=15; placebo n=15)

6 months

7.2 g/day

Blood samples from subjects taking either AGE or a placebo were mixed with compounds (epinephrine and collagen) to induce aggregation. AGE has shown 5-fold significant inhibition of epinephrine-induced platelet aggregation compared to placebo (p=0.003). Also, AGE showed 33% less platelet adhesion to fibrinogen after 3 months and 43% less after 6 months. The beneficial effects of AGE on lipids, blood pressure and platelet function provide a broad protection of cardiovascular system.

Inhibition of LDL-cholesterol Oxidation

Lau, B.H.S., 2001, J. Nutr.

131: 985S-988S

Double Blind Placebo Controlled Crossover Trial; n=16 (AGE n=8; placebo n=8)

2 weeks

3.6 g/day

Short term supplementation of AGE in human subjects has demonstrated an increased resistance of LDL to oxidation (p<0.05). The suppressed LDL oxidation may be one of the mechanisms for the beneficial effects of AGE in cardiovascular health.

Inhibition of LDL-cholesterol Oxidation

Munday, J. et al. 1999.

Atherosclerosis 143: 399-404.

3-arms Blind Crossover trial; n=9 (men n=4; women n=5)

1 week

2.4 g/day

Effect of AGE supplementation on the susceptibility of LDL-cholesterol to Cu2+-mediated oxidation was examined. LDL-cholesterol isolated from subjects given AGE was significantly more resistant to oxidation than control (37%).

Inhibition of Platelet Aggregation Blood Pressure Lowering

Inhibition of LDL-cholesterol Oxidation

STUDY

DESCRIPTION

DESIGN

DURATION

DOSAGE

MEASUREMENT AND RESULTS

Effect on Sickle Red Blood Cells

Ohnishi, S.T., et al. 2000.

Nutrition 16: 330-338.

Open Trial; n=20 (AGE n=10; control n=10)

6 months

6 g/day

A cocktail consisting of daily doses of 6 g of Aged Garlic Extract, 4-6 g of vitamin C and 800-1200 I.U. of vitamin E may be beneficial to patients with sickle cell anemia.

Effect on Sickle Red Blood Cells

Takasu J, et al., J. Nutr.

2006;136 Suppl 3:803S805S.

Open Trial; n=5 (men n=2; women n=3)

4 weeks

5 mL/day or equiv.

1.5g / day

The potential role of Aged Garlic Extract as an antioxidant for sickle red blood cells (RBC) was investigated.

Unanimously, the patient’s count of Heinz bodies decreased significantly from 58.9% to 29.8% during the 4 weeks of the study. This data suggests the significant antioxidant activity of Aged Garlic Extract on sickle cell anemia, and may represent a potential therapy to combat complications of the disease.

Takasu, J. et al. , 2002.

BMC Blood Disorders, 2:3 Reduction of Oxidative Stress during Exercise

Kimoto, R., et al., 2005.

Hokkaito J. Sports Med. Sci. 10:17-26

Open Trial; n=12 (AGE n=6; control n=6)

2 weeks

4 mL/day or equiv.

1.2g / day

Urinary 8-OHdG content during daily regular exercise was determined as an indicator of oxidative stress.

AGE significantly lowered the 8-OHdG content compared to the control group. The sum total of oxygen uptake during intense exercise after AGE supplementation was significantly increased. AGE may scavenge various oxidants by itself or up-regulate the antioxidant system, and thus AGE may consequently prevent the accumulation of oxidants during exercise.

Reduction of Oxidative Stress in Nonsmokers and Smokers

Dillon, S.A., et al., 2002. J. Nutr. 132: 168-171.

Open Trial; n=20 (smoker n=10; nonsmoker n=10)

2 weeks

5 mL/day or equiv.

1.5g / day

Plasma and urine levels of 8-iso-PGF2, an indicator of oxidative stress in smoking and nonsmoking individuals were determined. AGE reduced plasma and urine 8-iso-PGF2 by 29% and 37% in nonsmokers and by 35% and 48% in smokers. Thus, AGE may be useful in reducing oxidative stress in human.

Enhancement of Natural Killer (NK) Cell Activity in HIV+ patients

Abdullah, T.H., et al., 1989.

J. Oncology. 21: 52-53.

Open Trial n=7

12 weeks

5 g/day for 6 weeks+ 10 g/day for 6 weeks

After 6 weeks, 6 of 7 qualified patients had normal NK activity, and all had normal NK activity at 12 weeks.

Helper/suppressor ratio was improved in 4 of 7 patients. Conditions of diarrhea, genital herpes, candidiasis and pansinusitis with recurrent fever were also improved.

Modulation of Arachidonic acid Metabolism

Dimitrov, N.V., and Bennink, MR., 1997. In Nutraceuticals: Designer Food III Garlic, soy and Licorice. Paul P. Lachance (ed). Food & Nutrition Press., Trumbell, Ct., pp199-202.

Open Trial; n=8 (all women)

3 months

10mL/day or equiv.

3.0g / day

Compared to baseline, after 3 months of taking AGE, serum PGE2 levels were substantially decreased in majority of subjects. These results indicate that AGE is capable of modulating PGE2 and PGF2.

Prevention of Common Cold

Ushirotake, T., et al., 2004.

Rinshouiyaku. 20: 785-793.

Open Trial; n=272 (AGE n=154; control n=118)

2 mL/day or equiv.

0.6g / day

The frequency of catching colds was significantly decreased in the AGE group compared with the control group (P=0.002). Also, the disease days with symptoms of the common cold significantly shortened in AGE group compared to control (P=0.005). AGE prevents the common cold and shortens the diseased days.

Recovery from Cold with General Fatigue (Loss of Energy)

Kawashima, H., et al., 1985.

Shinryou to Shinyaku. 22: 3012-3024.

Open Trial; n=39 (men n=20; women n=19)

4 weeks

2 mL/day or equiv.

0.6g / day

Patients recovering from a cold taking an AGE preparation including vitamin B1, vitamin B12 and liver extract demonstrated significant improvement in 53.8% of patients and slightly effective or better in 89.7% patients.

A superb effectiveness was shown for chill (100%), abnormal pain (100%), general fatigue (loss of energy: 96.9%), myalgia (94.4%), and physical disorder (93.8%). The combination product promoted and enhanced the cold recovery process.

Recovery from Physical Fatigue (Loss of Energy)

Kawashima, H., et al., 1986. Kiso to Rinsho. 20: 8229-8245.

Placebo Controlled Trial; n=20 (AGE n=10; control n=10)

3 weeks

4mL/day or equiv.

1.2g / day

AGE improved patellar reflex level of both left and right legs, whereas the control group had worsened reflex level due to accumulation of physical fatigue. AGE may be effective for the prevention and recovery from fatigue.

Effects on Various Unexplained Complaints

Yaguchi, S., et al., 2005.

Shinryo to Shinyaku.

42:189-196

Open Trial; n=16 (men n=5; women n=11)

4 weeks

4 mL/day or equiv.

1.2g / day

Supplementation of AGE with other herbs showed >93.8% effect. In symptoms, recovery from physical fatigue (loss of energy), stiff shoulder, back pain and chill were significantly improved (p<0.05).

Effects on Various Unexplained Complaints

Miyoshi, A., et al., 1984.

Shinryou to Shinyaku.

21:1806-1820.

Open Trial; n=1008 (men n=476; women n=532)

4 weeks

2 mL/day or equiv.

0.6g / day

In 1,008 subjects, supplementation of AGE with vitamin B1, vitamin B12 and liver extract has shown its general efficacy: >57% moderate effective and >85.7% slight effective in improvement of symptoms were observed (56.1% general fatigue, 53% dizziness upon standing up, 52.8% dizziness, 52.2% debility, 51.1% anorexia, 49% lumbalgia, and 48.1% headache).

Contraindications - Risk Information There are no known contraindications. Not for use by pregnant or breastfeeding women, patients with pemphigus or prior to surgery.

Drug Interactions There are no known interactions with Kyolic® Aged Garlic ExtractTM and any prescribed medications or natural supplements. It is also reported that Kyolic® Aged Garlic ExtractTM does not reverse the effects of warfarin, an anti-coagulant, or over-accelerate the effects of aspirin and statin.* * References: Rozenfeld, V. et al. Double-blind , randomized, placebo- controlled trial of garlic in patients stabilized on warfarin therapy.

Eighteenth Annual Eastern States Conference for Pharmacy Residents and Preceptors. Baltimore, MD. April 21-24, 1999.

Macan, H. et al. Aged Garlic Extract may be safe for patients on Warfarin therapy. J. Nutrition 136: 793S-795S (2006).

Budoff, M., Aged garlic extract retards progression of coronary artery calcification. J. Nutriton136: 741S-744S (2006).

Side Effects Kyolic® Aged Garlic ExtractTM has been in the Japanese market as an over-the-counter drug for more than 50 years. It has been in the US market, as a dietary supplement, for 35 years and in Canada for the past 15 years, without side effects ever being reported.

Recommended Dose (Adults) Take one 600mg caplet daily with a meal or as directed by your health care practitioner.

MONOGRAPH Scientifically Proven Odourless Organic Garlic Supplement Go to www.rxkyolic.ca for more information on how to complete the pharmacists’ continuing education program “Impacting Cardiovascular Disease and Metabolic Syndrome with Aged Garlic Extract” for 2.0 CEUs - CCCEP File # 646-1107.

For more information on Kyolic® Aged Garlic ExtractTM, request copies of published research papers, or the continuing education study program, please call 1.877.929.2548 or visit www.kyolic.ca.

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