Reviewed: Ried K. Garlic lowers blood pressure in hypertensive subjects, improves arterial stiffness and gut microbiota: A review and meta-analysis. Exp Ther Med. February 2020;19(2):1472-1478. doi: 10.3892/etm.2019.8374.

Approximately one quarter of Western adults are affected by uncontrolled hypertension, and up to 62% of those taking standard blood pressure (BP) drugs have adverse effects (AEs), such as hypotension. Systematic reviews and meta-analyses (MAs) have indicated that garlic (Allium sativum, Amaryllidaceae) supplements, including Kyolic aged garlic extract (KAGE; Wakunaga, Ltd.; Mission Viejo, California), can reduce BP in patients with uncontrolled hypertension, defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg. KAGE previously was reported to reduce BP in patients with hypertension and not affect BP in normotensive subjects, which suggests that KAGE may have a BP-normalizing effect. The author conducted a systematic review of the effects of garlic on blood pressure and meta-analysis of its therapeutic activity in patients with hypertension. New evidence on the role B vitamins play in responsiveness of BP to garlic and the effects of KAGE on arterial stiffness and gut microbiota also are discussed.

Randomized, controlled trials (RCTs) with a minimum duration of two months and that were identified in previously published MAs were included. Additional RCTs published from 1955 through December 2018 were identified in MEDLINE. RCTs with normotensive subjects, garlic combination products, and dropout rates of > 30% were excluded. Mean SBP and DBP at baseline and the last follow-up visit were recorded. When more than one BP method was reported, sitting BP measurements were preferred over standing or supine measurements, and clinical measurements were preferred over ambulatory measurements. Mean differences in SBP and DBP were computed for garlic and control groups. Heterogeneity was assessed using the I2 statistic but is not discussed. Included RCTs in general were of high quality with minimum risk of bias. In five RCTs, deficiencies in reporting caused an unclear risk of bias in different areas.

Twelve RCTs (N = 553) met inclusion criteria, including two recent RCTs that were not included in previous MAs. A total of 533 patients had high SBP and 374 had high DBP. For trials with more than one intervention group, only the main arm was used to avoid double-counting placebo groups. Two recent RCTs were excluded from the MA for not including patients with hypertension and for testing a garlic-coriander (Coriandrum sativum, Apiaceae) seed product.

Garlic supplementation significantly reduced SBP by 8.32 ± 1.93 mmHg (P < 0.00001) and DBP by 5.48 ± 1.92 mmHg (P < 0.00001). According to the authors, an SBP reduction of 8-10 mmHg is estimated to reduce the risk of cardiovascular (CV) events such as heart attack, coronary artery disease, and stroke by 16-40%. Eight RCTs used one of three commercial garlic powders (GPs), and the other four RCTs used one of two KAGE products. Both KAGE products had comparable quantities of S-allyl cysteine (SAC), a stable vasoactive compound that is created from volatile sulfur compounds during the aging process of raw garlic.

In the latest study by the author’s research group,¹ KAGE reduced peripheral BP and central hemodynamic measures (central BP, pulse wave velocity, and pulse pressure). These are thought to be more predictive of CV events than peripheral SBP and DBP. Arterial stiffness, assessed via pulse wave velocity (PWV), increases with age due to loss of elastin and collagen fibers in the arterial walls. For every 10-year increase in age, PWV increases by an average of 1.43 m/sec. The study found that KAGE consumption was associated with an average PWV reduction of 0.7 m/sec after three months, leading the authors to conclude that KAGE has the potential to reverse arterial stiffness by five years.

In addition, KAGE consumption has been shown to improve the population density and diversity of gut microbiota, especially those in the Lactobacillus genus and Clostridia class. Microbiota dysbiosis (imbalance) has been linked to high BP in human and animal studies of hypertension, and consumption of probiotics has been found to produce significant reductions in BP.

Interestingly, BP was not significantly changed in 21 of 50 patients in one KAGE study.² Deficiencies of co-factors vital to garlic’s mechanisms of action, especially vitamins B₂, B₆, B₉, and B₁₂, may be a contributing factor. Garlic’s mechanisms of action are thought to involve two main signaling pathways via nitric oxide (NO) and hydrogen sulfide (H₂S) production; both require B vitamin co-factors.

KAGE also is reported to be able to normalize blood cholesterol levels, another CV risk factor. It normalizes blood viscosity without increasing risks of bleeding, in contrast to other dietary garlic supplementation, particularly raw garlic. The authors noted that larger, longer-term RCTs of KAGE are needed to further explore its effects on gut microbiota. Attention should be given to genetic and nutritional factors that may affect responsiveness.

References

1. Ried K, Travica N, Sali A. The effect of kyolic aged garlic extract on gut microbiota, inflammation, and cardiovascular markers in hypertensives: The GarGIC Trial. Front Nutr. 2018;5:122.
2. 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.