Reviewed: Ried K, Travica N, Sali A. The effect of aged garlic extract on blood pressure and other cardiovascular risk factors in uncontrolled hypertensives: the AGE at Heart trial. Integr Blood Press Control. 2016;9:9-21.
Editor’s note: This study was supported by a grant from Wakunaga of America Co., Ltd. The company also supplied the study capsules and provided funding for tests and research assistance; however, Wakunaga of America was not involved in the study design, data collection, analysis, or preparation of the manuscript.
Hypertension, or abnormally high blood pressure, is common around the world and is a risk factor for cardiovascular disease. Multiple clinical trials have reported that aged garlic extract (AGE; Allium sativum, Amaryllidaceae) lowers blood pressure. This randomized, double-blind, placebo-controlled trial investigated the effects of AGE on blood pressure, central hemodynamic measures (i.e., those of the central aortic region), and markers of cardiovascular function in adults with hypertension.
The trial was conducted by the National Institute of Integrative Medicine in Melbourne, Australia, between September 2013 and August 2014. Recruitment was directed at adults with “uncontrolled” hypertension, defined as systolic blood pressure (SBP) of at least 140 mmHg and/or diastolic blood pressure (DBP) of at least 90 mmHg. Ultimately, included patients had an SBP of at least 138 mmHg and/or a DBP of at least 85 mmHg. Participants were either not taking medication for hypertension or had been taking it for at least two months before the start of the trial, and their physicians did not plan to change their regimens during the trial. Exclusion criteria included serious health problems (e.g., terminal illness or dementia), secondary hypertension, pregnancy, and use of garlic supplements. Enrolled patients were randomly assigned to either the garlic group or placebo group and took two capsules per day in the evening with food for 12 weeks.
The treatment was Kyolic AGE, which contains 1.2 g of AGE powder standardized to 1.2 mg of S-allylcysteine (Reserve formula; Wakunaga of America Co., Ltd.; Mission Viejo, California). The AGE was processed by aging garlic at room temperature for 20 months, which has been shown to affect the concentrations of the potential bioactive compounds. The study article states that placebo capsules were matched to the AGE, but no other description is given. Activated carbon was used in packaging to minimize any difference in odor between the active treatment and placebo, though AGE is already less pungent than fresh garlic. Patients were instructed to keep their medication regimens constant and to keep a daily record of compliance.
Changes in blood pressure were measured at baseline and four, eight, and 12 weeks, and were the primary outcomes. At baseline, physical parameters, exercise, and stress levels were assessed via questionnaires. Central blood pressure (aorta blood pressure), pulse pressure, and other indicators of arterial stiffness (e.g., augmentation pressure) also were measured at baseline and four, eight, and 12 weeks. Fasting blood samples were collected at baseline and at 12 weeks to measure serum cholesterol and triglycerides, inflammation markers, and other parameters. Platelet function also was assessed as a gauge for AGE tolerability, particularly if patients used blood-thinning medications. The overall tolerability of AGE was measured by patient questionnaire.
From 185 patients screened, 104 were randomly assigned, with 55 patients in the AGE group and 49 patients in the placebo group. Following the baseline measurements, three patients in the AGE group and six patients in the placebo group withdrew from the study for personal reasons. At the end of the study, two patients in the AGE group and five patients in the placebo group were excluded due to low compliance (n = 3) or change in blood pressure medication regimen (n = 4, all in the placebo group). The final analysis included 50 patients in the AGE group and 38 patients in the placebo group.
Measurements were not significantly different between groups at baseline. On average, patients were 62.3 ± 11.3 years old and had a body mass index of 27.7 ± 4.9 kg/m2. Patient stress was “comparable” to population levels. In addition, 75% of participants used conventional drugs to treat high blood pressure, and some also used blood-thinning medication, drugs to decrease lipids, and treatments for diabetes and other diseases. At the end of the study, SBP decreased significantly more in the AGE group as compared with the placebo group (P = 0.016). This study included a separate analysis of those who had responded to the AGE treatment, which was defined as a decrease of more than 3% in SBP (at least 5 mmHg) or DBP (at least 3 mmHg). Based on this criteria, 50-60% of patients in the AGE group were considered responders. In this subgroup, there was a substantially greater decrease in SBP (change of 11.5 ± 1.9 mmHg) and DBP (change of 6.3 ± 1.1 mmHg) compared with placebo (P < 0.001 for both). “Non-responders” experienced a small, nonsignificant increase in both SBP and DBP.
Central SBP decreased more in the AGE group than in the placebo group, which approached significance (P = 0.05). Also, there were apparent trends in the AGE group, as compared to the placebo group, toward lowered central pulse pressure (P = 0.08), total vascular resistance (P = 0.06), and mean arterial pressure (P = 0.09) that approached significance. Those in the upper half of pulse wave velocity (PWV) showed a significantly greater velocity decrease in the AGE group as compared with the placebo group (P = 0.02). The change in tumor necrosis factor-(an inflammation marker) in the AGE group approached significance, as compared with the placebo group (P = 0.05), but this was mostly due to increased values in some patients in the placebo group. No other blood parameters were significantly affected throughout the study.
Compliance in included patients was 96.6 ± 5.6%. Approximately 36% of patients in the AGE group and 26% of patients in the placebo group experienced minor adverse effects such as heartburn, gas, and bloating, mostly during the first week of the study. (A few, mostly in the AGE group, also reported better digestion.) Platelet function, if abnormal, tended to normalize when garlic was taken, while normal function was not affected; there was no interaction with blood-thinning pharmaceuticals.
This study suggests benefits of AGE for hypertension in certain patients, with greater benefit in patients who have more severe pathology. The authors hypothesize that the different patient responses to AGE may be due to individuality; this phenomenon has been reported previously. Certain bioactive compounds in AGE may modulate cellular signaling upstream of vascular function, and bioactivity may be impacted by diet, vitamin status, or genetics. Stated limitations of this study include a greater amount of dropouts in the placebo group, relatively small sample size, and the potential impact of other medications, although it is stated that certain variables were controlled in the statistical analysis. It is also mentioned that additional studies are necessary to clarify effects of AGE on central hemodynamic measures and the causes of inter-individual variability.
—Amy C. Keller, PhD