Ried K, Frank OR, Stocks NP. Aged garlic extract reduces blood pressure in hypertensives: a dose-response trial. Eur J Clin Nutr. 2013 Jan;67(1):64-70.
Randomized, placebo-controlled, double-blind trial of 12 weeks duration
Participants and Study Design
A total of 79 participants were allocated into 4 groups treated with either aged garlic extract (AGE) and S-allylcysteine (groups g1, g2 and g4 containing 240/480/960 mg of AGE and 0.6/1.2/2.4 mg of S-allylcysteine) or placebo based on 80% power analysis to detect 10 mmHg of difference in systolic blood pressure. These participants were on an established plan of prescription antihypertensive medications for the 2 months prior to enrolling in the trial.
The primary outcome was to detect significant difference in systolic blood pressure in 3 treatment groups (g1, g2 and g4) compared to placebo at 4, 8 and 12 weeks. The secondary outcome was to determine tolerability and acceptability of the supplements.
There was a significant reduction in systolic blood pressure among participants in the g2 group compared to the placebo over 12 weeks (-11.8±5.4 mmHg, P=0.006), whereas it reached borderline statistically significant reduction in the group g4 at 8 weeks (-7.4±4.1 mmHg, P=0.07). There was improvement in diastolic blood pressure in the g2 group, though it was statistically insignificant compared to placebo (-5.3±4.2 mmHg). Gastrointestinal intolerance was the main side effect, especially among group g4 participants. The pills were easy to take and acceptable to most participants.
Multiple randomized clinical trials have shown cardioprotective effects of AGE. The current clinical trial provides further evidence of the role of AGE in lowering blood pressure among hypertensive patients. According to Reid K and colleagues, "The observed reduction in systolic blood pressure is comparable to that achieved with commonly prescribed antihypertensive medicines, and is of clinical significance, whereby a reduction of about 10 mmHg in SBP is associated with a risk reduction in cardiovascular disease by 16–40%."
The benefit was greatest with the 480 mg preparation of AGE, whereas the antihypertensive effect was smaller with the 960 mg preparation of AGE, perhaps due to poor compliance and less tolerability associated in the g4 group. In another randomized clinical trial, Reid K et al. showed a significant reduction in systolic blood pressure (-10.2±4.3 mmHg, P=0.03) associated with the use of 960 mg of AGE and 2.4mg of S-allylcysteine in participants with baseline systolic blood pressure greater than ≥140 mmHg. The current study showed a borderline significant reduction of systolic blood pressure in the g4 group (-7.4±4.1 mmHg, P=0.07). Further large-scale studies may be required to validate these findings.
Cardiovascular disease is the leading cause of morbidity and mortality among the US population. AGE helps to modulate multiple cardiovascular risk factors by lowering blood pressure, inhibiting platelet aggregation and adhesion, lowering cholesterol, and preventing LDL oxidation and smoking-induced oxidative damage.1–4 Our previous studies have shown that AGE retards the progression of coronary atherosclerosis, improves vascular function, and has favorable a effect on oxidative biomarkers among high-risk firefighter populations.5–8 AGE has been proposed to effect coronary atherosclerosis by preventing smooth muscle cell transformation and proliferation, preventing entry of lipids into the arterial wall and macrophages, and also directly suppressing atherosclerosis.2,9 AGE has also been shown to have a beneficial effect on arterial function by inhibiting endothelial cell damage, transforming smooth muscle cells, and inhibiting the damage of nitric oxide synthesis.10,11
Cardiovascular disease is the leading cause of morbidity and mortality among the US population.
AGE was shown to have promising effects on systolic blood pressure reduction among group g2 participants in this study. The effect on diastolic blood pressure could not reach statistical significance due to limited power to detect significant changes in diastolic blood pressure. Similarly, the analysis could not be powered by the type of antihypertensive medications. The results from this trial will have far-reaching consequences and provide a scientific evidence for the use of AGE for its antihypertensive effects, especially among patients who are interested in using supplements to control blood pressure. Reid and colleagues showed "AGE to be an effective and tolerable treatment in uncontrolled hypertension," stating it "may be considered as a safe adjunct treatment to conventional antihypertensive therapy." Further large studies can be performed to confirm these findings and to answer questions that could not be answered in this trial, including the effect of AGE on diastolic blood pressure, to determine whether the antihypertensive effect of AGE is different in combination with different antihypertensive classes of medications, and to evaluate the effect of AGE on long-term cardiovascular morbidity and mortality.
- Steiner M, Khan AH, Holbert D, Lin RI. A double-blind crossover study in moderately hypercholesterolemic men that compared the effect of aged garlic extract and placebo administration on blood lipids. Am J Clin Nutr. 1996;64(6):866-870.
- Campbell JH, Efendy JL, Smith NJ, Campbell GR. Molecular basis by which garlic suppresses atherosclerosis. J Nutr. 2001;131(3s):1006S-1009S.
- Okuhira M HH, Sandhu R, Steiner M. Modication of cardiovascular risk factors aged garlic extract (AGE). Phytomedicine. 2000;7:49-50.
- Rahman K, Billington D. Dietary supplementation with aged garlic extract inhibits ADP-induced platelet aggregation in humans. J Nutr. 2000;130(11):2662-2665.
- Budoff MJ, Takasu J, Flores FR, et al. Inhibiting progression of coronary calcification using Aged Garlic Extract in patients receiving statin therapy: a preliminary study. Prev Med. 2004;39(5):985-991.
- Budoff MJ, Ahmadi N, Gul KM, et al. Aged garlic extract supplemented with B vitamins, folic acid and L-arginine retards the progression of subclinical atherosclerosis: a randomized clinical trial. Prev Med. 2009;49(2-3):101-107.
- Zeb I, Ahmadi N, Nasir K, et al. Aged garlic extract and coenzyme Q10 have favorable effect on inflammatory markers and coronary atherosclerosis progression: A randomized clinical trial. J Cardiovasc Dis Res. 2012;3(3):185-190.
- Larijani VN, Ahmadi N, Zeb I, Khan F, Flores F, Budoff M. Beneficial effects of aged garlic extract and coenzyme Q10 on vascular elasticity and endothelial function: the FAITH randomized clinical trial. Nutrition. 2013;29(1):71-75.
- Gonen A, Harats D, Rabinkov A, et al. The antiatherogenic effect of allicin: possible mode of action. Pathobiology. 2005;72(6):325-334.
- Ho SE, Ide N, Lau BH. S-allyl cysteine reduces oxidant load in cells involved in the atherogenic process. Phytomedicine. 2001;8(1):39-46.
- Morihara N, Sumioka I, Moriguchi T, Uda N, Kyo E. Aged garlic extract enhances production of nitric oxide. Life Sci. 2002;71(5):509-517.