Chios Mastic Gum Fails to Lower Blood Pressure in Controlled Hypertension Trial

Chios mastic, the aromatic resin harvested from the bark of Pistacia lentiscus var. Chia trees on the Greek island of Chios, has been prized for millennia as a chewing gum, a digestive remedy and a flavoring for sweets and breads. In recent years, laboratory and early clinical studies suggested it might also do something far more consequential: lower blood pressure and reduce the residual cardiovascular risk that lingers even in patients whose hypertension appears to be well managed. Now, one of the most rigorous tests of that idea to date has delivered a sobering but scientifically revealing verdict. The HYPER-MASTIC randomized controlled trial, conducted at the Department of Clinical Therapeutics of Alexandra General Hospital in Athens, found that three months of mastic supplementation did not reduce blood pressure in people with stable, well-controlled hypertension, even though the resin produced measurable changes in vascular gene expression among patients at higher cardiovascular risk.

The trial, published in Pharmacology Research & Perspectives, addressed a stubborn clinical problem. Hypertension remains the most prevalent modifiable risk factor for cardiovascular disease, and bringing blood pressure under control with medication dramatically reduces that risk. Yet studies consistently show that 20 to 40 percent of cardiovascular risk persists in well-controlled hypertensive patients, a phenomenon researchers call residual risk. Scientists attribute this stubborn remainder to chronic inflammation, oxidative stress, endothelial dysfunction, arterial stiffness and genetic and epigenetic factors, including microRNA-21, a small regulatory RNA implicated in hypertensive vascular remodeling. Standard antihypertensive drugs do not fully neutralize these pathways, which is why nutraceuticals with antioxidant and anti-inflammatory properties have attracted attention as potential adjuncts.

Chios mastic was a plausible candidate. The resin contains characteristic triterpenes, notably masticadienonic acid and isomasticadienonic acid, and preclinical work has documented antioxidant, anti-inflammatory and cardioprotective effects. An earlier human study by Kontogiannis and colleagues reported an acute antihypertensive effect and hinted at mechanisms involving proteostasis, the cellular system that degrades oxidized and misfolded proteins, and the control of reactive oxygen species. The HYPER-MASTIC team hypothesized that sustained mastic supplementation might chip away at residual cardiovascular risk in treated hypertensive patients, and designed a double-blind, placebo-controlled, parallel-group trial to find out.

Between April 2022 and February 2024, the researchers enrolled 105 participants aged 40 to 80 with stable, well-controlled hypertension confirmed by 24-hour ambulatory monitoring. Volunteers were randomized to receive 1500 milligrams per day of mastic, 2800 milligrams per day, or matching placebo for three months. Blinding was unusually thorough: placebo tablets were identical in size and shape and were sprayed with mastic scent to preserve the illusion. Participants attended four study visits, during which the team measured 24-hour ambulatory peripheral and central blood pressure, pulse wave velocity as a gold-standard index of arterial stiffness, endothelial function via flow-mediated dilatation, carotid and femoral artery ultrasound, and echocardiographic cardiac function. Blood sampling tracked reactive oxygen species and proteasome activity in immune cells and red blood cells, and RNA sequencing captured transcriptomic changes in a predefined high-risk subgroup of 59 participants.

The primary result was unambiguous. Changes in 24-hour systolic and diastolic blood pressure, the trial’s primary endpoints, did not differ significantly between the mastic and placebo groups. The low-dose group showed some statistically significant within-group increases in pulse wave velocity and central blood pressure parameters, but these did not translate into significant time-by-group interactions, with the single exception of 24-hour central systolic pressure, where a trend toward an increase in the low-dose group emerged. Office diastolic pressure rose slightly in the high-dose group, and flow-mediated dilatation barely changed anywhere. In short, mastic conferred no additional short-term antihypertensive benefit in these patients.

Crucially, the researchers could rule out poor adherence as an explanation. Participants kept daily diaries, received biweekly follow-up calls, and, most persuasively, plasma levels of the mastic triterpenes masticadienonic and isomasticadienonic acid were measured objectively. These metabolites rose in the low-dose group and climbed roughly three-fold further in the high-dose group while remaining flat under placebo, confirming that participants were genuinely taking their supplements. The supplement was also well tolerated, with no serious adverse events reported across the three arms.

The molecular assays told a similar story of neutrality. Reactive oxygen species and proteasome activity in peripheral blood mononuclear cells and red blood cells showed no significant differences between groups at baseline or at three months, contrasting with the effects seen in earlier acute and experimental studies. The authors suggest this likely reflects a ceiling effect: participants whose blood pressure and metabolic risk factors were already well controlled simply carried a low inflammatory and oxidative burden, leaving little room for mastic to improve. This pattern echoes findings from other nutraceutical trials, including studies of quercetin and resveratrol, where blood pressure effects shrink or vanish in lower-risk populations, and from the earlier MAST4HEALTH trial, in which mastic improved metabolic and inflammatory markers most clearly in people with greater baseline cardiometabolic burden.

Where the trial did find something intriguing was at the level of gene expression. In the high-risk subgroup, defined by criteria such as elevated C-reactive protein, advanced age, chronic renal failure or residual blood pressure elevation, RNA sequencing of whole blood revealed a distinct set of differentially expressed genes after mastic supplementation compared with placebo. Only about one percent of altered genes overlapped between the mastic and placebo arms, with 141 genes uniquely changed by mastic. Functional enrichment analysis showed that the upregulated genes clustered in pathways governing tight junction organization and cellular adhesion, processes central to endothelial barrier integrity and vascular permeability that are disrupted in hypertension. The authors interpret this as evidence that mastic may support endothelial stability and vascular homeostasis even when it does not move the blood pressure needle, a mastic-specific biological effect supported by the absence of comparable transcriptomic changes under placebo. Complementary analyses from the same project also found modulation of microRNA-21, an epigenetic marker of vascular remodeling, particularly in relation to night-time blood pressure.

The investigators are careful about the caveats. The low-dose group was significantly younger than the placebo group and reported family history of hypertension more often, imbalances that were adjusted for statistically but that may have contributed to vascular variability. A three-month intervention may be too brief for gradual nutraceutical effects to emerge, and the well-controlled baseline state of the cohort itself limited the opportunity to detect additive benefits. The authors also emphasize that mastic was studied as a nutraceutical supplement and is not approved by regulators for treating hypertension or reducing cardiovascular risk, so patients should not view the resin as a substitute for prescribed therapy.

The takeaway from HYPER-MASTIC is a nuanced one that resists the simple narrative of a miracle supplement. Chios mastic, at 1500 or 2800 milligrams daily for three months, does not lower blood pressure in people whose hypertension is already well managed, and the trial’s rigorous design, objective adherence verification and comprehensive vascular phenotyping make that null result difficult to dismiss. Yet the resin’s ability to shift expression of genes involved in endothelial integrity in higher-risk patients suggests that its biological activity is real and may be most relevant where inflammatory and metabolic burden is greatest. The authors call for longer trials in higher-risk populations with integrated molecular and clinical endpoints to determine whether mastic’s transcriptomic fingerprints translate into fewer heart attacks and strokes. For now, the ancient resin of Chios remains what it has long been: a fascinating natural product with genuine biological activity, still awaiting proof that it can protect the cardiovascular system in the patients who need it most.

Subject of Research: Effects of Chios mastic gum supplementation on blood pressure and vascular biology in well-controlled hypertension

Article Title: Chios Mastic in Well‐Controlled Hypertension: Findings From the HYPER‐MASTIC Randomized Controlled Trial

Article References: Kalafati, I. P., Kyriazopoulou‐Korovesi, A.-A., Mentsiou‐Nikolaou, E., Papaioannou, M., Konstantaki, C., Angelidakis, L., Gianniou, D. D., Mikropoulou, E. V., Giardoglou, P., Valakos, D., Vatsellas, G., HYPER‐MASTIC Consortium, Andreadou, I., Manios, E., Halabalaki, M., Trougakos, I. P., Dedoussis, G. V., & Stamatelopoulos, K. (2026). Chios Mastic in Well‐Controlled Hypertension: Findings From the HYPER ‐ MASTIC Randomized Controlled Trial. Pharmacology Research & Perspectives, 14(6), Article e70322. https://doi.org/10.1002/prp2.70322

Image Credits: AI Generated

DOI: 10.1002/prp2.70322

Keywords: Chios mastic, hypertension, randomized controlled trial, cardiovascular risk, blood pressure, endothelial function, oxidative stress, nutraceutical, Pistacia lentiscus, RNA sequencing, arterial stiffness, residual cardiovascular risk