Life Extension Magazine®
Heart disease is the world's leading cause of death.1,2 Yet many of the risk factors associated with it are largely preventable or controllable through changes in diet or nutrition.3
Pomegranate is a nutrient-dense superfood that has been consumed for millennia and has become popular all over the world.4 It is packed with compounds that have been shown in preclinical models to possess antioxidant and anti-inflammatory effects.4,5
One of its most impressive properties demonstrated in preclinical settings is its ability to protect the heart in multiple ways, including by preventing and even reversing endothelial dysfunction6-- a major contributor to atherosclerosis, the buildup of plaque in the arteries.7
Its benefits for the heart are enormous. Across many different kinds of studies, pomegranate extracts have been found to reduce blood clots in animals,8 reduce cholesterol and triglycerides in animals,9 improve blood flow in young healthy adults,10 and lower blood pressure in humans.11,12
In a clinical trial, pomegranate has been shown to reverse atherosclerotic changes in patients with carotid artery stenosis.11
These benefits may reduce risks for cardiovascular diseases.
A Nutritional Powerhouse
Pomegranate has been recognized as one of the oldest known edible fruits.4
All parts of the pomegranate plant, including the fruit, leaves, peel, seeds, and flowers, are packed with beneficial compounds. These include anthocyanins, organic acids, flavonoids, and tannins.4
These potent bioactive compounds, found in pomegranate fruit, juice, and extracts have been shown to have health-promoting properties, with the potential to help improve or control inflammation, diabetes, blood lipid levels, and more. A number of clinical trials have confirmed the benefits, especially for blood pressure.4
By preventing and reversing endothelial dysfunction, pomegranate may help protect the cardiovascular system against the life-threatening processes that lead to high blood pressure, atherosclerosis, and eventually heart attacks and strokes.4,6
Endothelial dysfunction affects the delicate tissue (endothelium) lining the inside of blood vessels. It is a major contributor to atherosclerosis, the buildup of plaque in the arteries. Atherosclerosis, in turn, is the leading cause of heart disease, heart attacks, and strokes.7,13
Improving Lipid Health
Atherosclerosis is a complex process that involves inflammation, endothelial dysfunction, and active lipid accumulation. There is convincing evidence that cholesterol-lowering drugs, targeting low density lipoprotein (LDL) and related particles, can reduce progression of plaque and prevent cardiovascular events.14
Animal models have shown that pomegranate can reduce blood levels of total cholesterol, LDL cholesterol (the "bad" kind that contributes to atherosclerosis), and triglycerides (another type of fat linked to risk for heart disease).15-18
Oxidation of LDL cholesterol makes it even more dangerous than normal LDL. Oxidized LDL accumulates in blood vessel walls more easily and accelerates the progression of atherosclerosis. Pomegranate decreases the oxidation of lipids.19,20
In human studies, consuming pomegranate juice has significantly reduced blood levels of oxidized LDL.19,21
How Endothelial Dysfunction Leads to Heart Disease
Many people think of blood vessels as the body's pipes, passively carrying blood through them. Nothing could be further from the truth.
Blood vessels are active structures that play as big a role in blood supply as the heart itself. The blood vessels pulse and move with each heartbeat and actively change their diameter in response to the body's demands. This helps maintain normal blood pressure and adequate blood flow.
The endothelium is a single layer of cells that lines the inner wall of every blood vessel. It produces signaling compounds and responds to chemical and physical signals, helping to control vascular reactivity (the vessel's response to a stimulus).13
When functioning optimally, the endothelium helps regulate blood vessels' tone, size, and function.
Vascular health depends on a balance between signals that cause blood vessels to dilate (widen) and other signals that cause them to constrict (narrow).13
This is particularly true in the arteries, the blood vessels that carry blood away from the heart to most tissues of the body.
Unfortunately, the endothelium can become damaged with advancing age. Other factors, including oxidative stress, inflammation, high blood pressure, and elevated blood glucose, can also harm the endothelium, impairing its ability to dilate. Narrowed and inflexible arteries can reduce vital blood flow.6,22
This endothelial dysfunction is a direct contributor to high blood pressure and the development of atherosclerosis, the cause of almost all heart disease.22
Restoring Blood Vessel Function
Perhaps the most important sign of endothelial dysfunction is an impaired ability of blood vessels to dilate (widen) when necessary.22
Both preclinical and clinical evidence demonstrate that pomegranate extract improves endothelial function and promote arterial relaxation and dilation.23,24
Pomegranate accomplishes this by targeting several compounds, including:
- Nitric oxide. This is one of the most important vasodilators, which means it induces the dilation of arteries. In preclinical studies, scientists have found that pomegranate is supportive of vascular/endothelial health through a dual-action of increasing the enzymes that support nitric oxide production22,25-27 but also neutralizing compounds, such as peroxynitrate, an enzyme that can be damaging to nitric oxide production.28
- Thromboxane A2. This vasoconstrictor causes the narrowing of arteries.29 Pomegranate extract inhibits an enzyme required to produce thromboxane A2,30 lowering its levels and reducing constriction of arteries.
Preventing Blood Clots
Endothelial dysfunction and atherosclerosis increase the risk of abnormal blood clots. Most heart attacks and strokes are caused by clots forming in diseased arteries, which reduces blood flow to the heart or brain.14,31
Fortunately, the same thromboxane that is blocked by pomegranate also influences the function of platelets, the tiny cells in our blood that form clots.
Thromboxane A2 activates platelets and causes their aggregation. Pomegranate reduces thromboxane A2.29,30
In animal studies, pomegranate juice and extract reduces the clotting of human platelets, even when exposed to stimuli that would normally cause their aggregation.8,30
What You Need to Know
Pomegranate Improves Endothelial Health
- Heart disease is the most common cause of death worldwide.
- Endothelial dysfunction, damage to the layer of cells lining the inside of arteries, is a major contributor to atherosclerosis and risk for cardiovascular disease.
- Pomegranate and its extracts contain many antioxidant and anti-inflammatory nutrients that can shield against a wide range of chronic age-related diseases.
- Many of the health benefits of pomegranate apply specifically to blood vessel health, protecting against endothelial dysfunction and atherosclerosis in animal and human studies. This reduces the risk of developing cardiovascular disease.
- Even in subjects already experiencing signs of heart disease, pomegranate intake has been shown to reduce symptoms.
Improving Blood Pressure
High blood pressure is a contributor to initiation and development of atherosclerosis.32
One of the most common classes of drugs used to lower blood pressure are ACE inhibitors, which block an enzyme involved in blood pressure.
Preclinical and clinical research discovered that, like these medications, pomegranate inhibits ACE activity.33,34 Through this and other mechanisms, it is able to help reduce elevated blood pressure, thereby protecting blood vessel health and lowering the risk of heart disease.12
In people with high blood pressure, two weeks of pomegranate intake decreased blood ACE activity by 36%.33 In this and other human studies, pomegranate led to a significant reduction in both systolic (top number) and diastolic (bottom number) blood pressure.12,35
In one study of subjects with atherosclerosis in the carotid artery, which delivers blood to the brain, head, and neck, pomegranate juice intake reduced systolic blood pressure up to 12%.11
Those with high blood pressure should use an at-home blood pressure monitor to target blood pressure below 120/80 throughout the day and night.
With aging, anti-hypertension drugs are often required in addition to lifestyle changes to achieve optimal blood pressure readings.
Controlling Blood Glucose
Poor control of blood glucose levels is another powerful contributor to endothelial dysfunction and atherosclerosis.6,13
In animal studies, pomegranate seed-oil extract improved insulin sensitivity and reduced fasting blood glucose levels.36,37 In studies of patients with type II diabetes or impaired glucose control, pomegranate juice improved pancreas function, insulin sensitivity, and blood glucose control.38,39
Pomegranate extract has been shown to suppress the glycation of proteins and prevent their accumulation, even in a high sugar diet.40 Glycation is a chemical reaction whereby sugars permanently attach themselves to proteins, fats, or nucleic acids. This is a highly destructive process that damages tissues, including those in the arteries.41
Reducing Atherosclerotic Plaques
Through all these actions, pomegranate use has a profound impact on blood vessel health.
In studies of rodents and pigs, pomegranate extract is capable of reversing endothelial dysfunction.42,43
Animal models of accelerated atherosclerosis also show that pomegranate prevents and reverses the progression of atherosclerotic plaque.
For example, rodent studies showed that pomegranate juice or extract helped maintain healthy arteries and significantly slowed the progression of atherosclerosis.44,45 In a mouse study, pomegranate reduced the size of atherosclerotic plaques by 44%.21
Human trials have also found striking effects on cardiovascular disease outcomes.
One clinical study that evaluated patients with atherosclerosis in the carotid arteries found that pomegranate juice consumption decreased the extent of atherosclerotic plaque by up to 35% after a year. Those who did not receive pomegranate had a 9% worsening of atherosclerosis.11
In adults hospitalized with unstable angina (chest pain at rest due to inadequate blood flow) or heart attack, one glass of pomegranate juice per day for five days, as an add-on to standard treatment, significantly reduced the frequency, intensity, and duration of angina (chest pain) episodes. It also reduced levels of a marker of oxidative stress.46
Another study in patients with heart disease found that while exercise-induced ischemia (reduced blood flow) of the heart increased in a control group over three months, patients receiving pomegranate had a significant decrease.47
These studies show how pomegranate can help reduce risk for atherosclerosis and cardiovascular disease and help people with existing heart disease.
Summary
Pomegranate is a rich natural source of antioxidant and anti-inflammatory nutrients. Extracts of pomegranate have been found to help reduce risk factors for atherosclerosis and cardiovascular disease.
Pomegranate and its extracts may be capable of preventing and reversing signs of endothelial dysfunction, blood vessel damage that contributes to atherosclerosis and cardiovascular events like heart attack and stroke.
Pomegranate also improves other risk factors that contribute to cardiovascular disease, including blood pressure, blood glucose, and oxidation of lipids.
Through all of these actions, pomegranate and its extracts could reduce the risk of cardiovascular disorders and relieve symptoms in people already diagnosed with heart disease.
If you have any questions on the scientific content of this article, please call a Life Extension Wellness Specialist at 1-866-864-3027.
References
- Benjamin EJ, Virani SS, Callaway CW, et al. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation. 2018 Mar 20;137(12):e67-e492.
- Available at: https://newsroom.heart.org/news/more-than-half-of-u-s-adults-dont-know-heart-disease-is-leading-cause-of-death-despite-100-year-reign. Accessed March 27, 2024.
- Available at: https://www.cdc.gov/chronicdisease/resources/publications/aag/heart-disease-stroke.htmhttps://world-heart-federation.org/what-we-do/prevention/. Accessed March 27, 2024.
- Wang D, Ozen C, Abu-Reidah IM, et al. Vasculoprotective Effects of Pomegranate (Punica granatum L.). Front Pharmacol. 2018;9:544.
- Emami Kazemabad MJ, Asgari Toni S, Tizro N, et al. Pharmacotherapeutic potential of pomegranate in age-related neurological disorders. Front Aging Neurosci. 2022;14:955735.
- Delgado NTB, Rouver WN, Dos Santos RL. Protective Effects of Pomegranate in Endothelial Dysfunction. Curr Pharm Des. 2020;26(30):3684-99.
- Medina-Leyte DJ, Zepeda-Garcia O, Dominguez-Perez M, et al. Endothelial Dysfunction, Inflammation and Coronary Artery Disease: Potential Biomarkers and Promising Therapeutical Approaches. Int J Mol Sci. 2021 Apr 8;22(8):3850.
- Riaz A, Khan RA. Anticoagulant, antiplatelet and antianemic effects of Punica granatum (pomegranate) juice in rabbits. Blood Coagul Fibrinolysis. 2016 Apr;27(3):287-93.
- Bagri P, Ali M, Aeri V, et al. Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxida- tion and antioxidant enzymes in experimental diabetes. Food Chem Toxicol. 2009 Jan;47(1):50-4.
- Roelofs EJ, Smith-Ryan AE, Trexler ET, et al. Effects of pomegranate extract on blood flow and vessel diameter after high-intensity exer- cise in young, healthy adults. Eur J Sport Sci. 2017 Apr;17(3):317-25.
- Aviram M, Rosenblat M, Gaitini D, et al. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin Nutr. 2004 Jun;23(3):423-33.
- Sahebkar A, Ferri C, Giorgini P, et al. Effects of pomegranate juice on blood pressure: A systematic review and meta-analysis of randomized controlled trials. Pharmacol Res. 2017 Jan;115:149-61.
- Xu S, Ilyas I, Little PJ, et al. Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies. Pharmacol Rev. 2021 Jul;73(3):924-67.
- Palasubramaniam J, Wang X, Peter K. Myocardial Infarction-From Atherosclerosis to Thrombosis. Arterioscler Thromb Vasc Biol. 2019Aug;39(8):e176-e85.
- Bagri P, Ali M, Aeri V, et al. Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Food Chem Toxicol. 2009Jan;47(1):50-4.
- Hossin FLA. Effect of pomegranate (Punica granatum) peels and it's extract on obese hypercholesterolemic rats. Pakistan Journal of Nutrition. 2009;8(8):1251-7.
- Lei F, Zhang XN, Wang W, et al. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. Int J Obes (Lond). 2007 Jun;31(6):1023-9.
- Neyrinck AM, Van Hee VF, Bindels LB, et al. Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: potential implication of the gut microbiota. Br J Nutr. 2013 Mar 14;109(5):802-9.
- Sohrab G, Ebrahimof S, Sotoudeh G, et al. Effects of pomegranate juice consumption on oxidative stress in patients with type 2 diabetes: a single-blind, randomized clinical trial. Int J Food Sci Nutr. 2017 Mar;68(2):249-55.
- MacRae F Linton M, Patricia G Yancey, PhD, Sean S Davies, PhD, W. Gray Jerome, PhD, Edward F Linton, MD, Wenliang L Song, MD, Amanda C Doran, PhD, MD, and Kasey C Vickers, PhD. The Role of Lipids and Lipoproteins in Atherosclerosis. 2019.
- Aviram M, Dornfeld L, Rosenblat M, et al. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications to LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. Am J Clin Nutr. 2000 May;71(5):1062-76.
- Sun HJ, Wu ZY, Nie XW, Bian JS. Role of Endothelial Dysfunction in Cardiovascular Diseases: The Link Between Inflammation and Hydrogen Sulfide. Front Pharmacol. 2019;10:1568.
- Anwaier G, Lian G, Ma GZ, et al. Punicalagin Attenuates Disturbed Flow-Induced Vascular Dysfunction by Inhibiting Force-Specific Activation of Smad1/5. Front Cell Dev Biol. 2021;9:697539.
- Roelofs EJ, Smith-Ryan AE, Trexler ET, et al. Effects of pomegranate extract on blood flow and vessel diameter after high-intensity exercise in young, healthy adults. Eur J Sport Sci. 2017 Apr;17(3):317-25.
- Delgado NT, Rouver WD, Freitas-Lima LC, et al. Pomegranate Extract Enhances Endothelium-Dependent Coronary Relaxation in Isolated Perfused Hearts from Spontaneously Hypertensive Ovariectomized Rats. Front Pharmacol. 2016;7:522.
- Omar U, Aloqbi A, Yousr M, Howell NK. Punicalagin induce the production of nitric oxide and inhibit angiotensin converting enzyme in endothelial cell line EA.hy926. Universal Journal of Public Health. 2016;4(5):268-77.
- Omar U, Aloqbi A, Yousr M, K. Howell N. Punicalagin Induce the Production of Nitric Oxide and Inhibit Angiotensin Converting Enzyme in Endothelial Cell Line EA.hy926. Universal Journal of Public Health. 2016 09/01;4(5):268-77.
- Cervantes-Anaya N, Azpilcueta-Morales G, Estrada-Camarena E, et al. Pomegranate and Its Components, Punicalagin and Ellagic Acid, Promote Antidepressant, Antioxidant, and Free Radical-Scavenging Activity in Ovariectomized Rats. Front Behav Neurosci. 2022;16:836681.
- Brainard BM. Antiplatelet Drugs. In: Silverstein DC, Hopper K, editors. Small Animal Critical Care Medicine. St. Louis: W.B. Saunders; 2015:877-82.
- Mattiello T, Trifiro E, Jotti GS, Pulcinelli FM. Effects of pomegranate juice and extract polyphenols on platelet function. J Med Food. 2009 Apr;12(2):334-9.
- Available at: https://www.hopkinsmedicine.org/health/conditions-and-diseases/stroke/types-of-stroke. Accessed March 28, 2024.
- Gallo G, Volpe M, Savoia C. Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications. Front Med (Lausanne). 2021;8:798958.
- Aviram M, Dornfeld L. Pomegranate juice consumption inhibits serum angiotensin converting enzyme activity and reduces systolic blood pressure. Atherosclerosis. 2001 Sep;158(1):195-8.
- Dos Santos RL, Dellacqua LO, Delgado NT, et al. Pomegranate peel extract attenuates oxidative stress by decreasing coronary angiotensin-converting enzyme (ACE) activity in hypertensive female rats. J Toxicol Environ Health A. 2016;79(21):998-1007.
- Asgary S, Sahebkar A, Afshani MR, et al. Clinical evaluation of blood pressure lowering, endothelial function improving, hypolipidemic and anti-inflammatory effects of pomegranate juice in hypertensive subjects. Phytother Res. 2014 Feb;28(2):193-9.
- Harzallah A, Hammami M, Kepczynska MA, et al. Comparison of potential preventive effects of pomegranate flower, peel and seed oil on insulin resistance and inflammation in high-fat and high-sucrose diet-induced obesity mice model. Arch Physiol Biochem. 2016;122(2):75-87.
- Sun YL, Zhou FM, Wang HR. Mechanism of pomegranate ellagic polyphenols reducing insulin resistance on gestational diabetes mellitus rats. Am J Transl Res. 2019;11(9):5487-500.
- Banihani SA, Fashtaky RA, Makahleh SM, et al. Effect of fresh pomegranate juice on the level of melatonin, insulin, and fasting serum glucose in healthy individuals and people with impaired fasting glucose. Food Sci Nutr. 2020 Jan;8(1):567-74.
- Banihani SA, Makahleh SM, El-Akawi Z, et al. Fresh pomegranate juice ameliorates insulin resistance, enhances beta-cell function, and decreases fasting serum glucose in type 2 diabetic patients. Nutr Res. 2014 Oct;34(10):862-7.
- Kumagai Y, Nakatani S, Onodera H, et al. Anti-Glycation Effects of Pomegranate (Punica granatum L.) Fruit Extract and Its Components in Vivo and in Vitro. J Agric Food Chem. 2015 Sep 9;63(35):7760-4.
- Kim CS, Park S, Kim J. The role of glycation in the pathogenesis of aging and its prevention through herbal products and physical exercise. J Exerc Nutrition Biochem. 2017 Sep 30;21(3):55-61.
- Liu X, Cao K, Lv W, et al. Punicalagin attenuates endothelial dysfunction by activating FoxO1, a pivotal regulating switch of mitochondrial biogenesis. Free Radic Biol Med. 2019 May 1;135:251-60.
- Vilahur G, Padro T, Casani L, et al. Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway. Rev Esp Cardiol (Engl Ed). 2015 Mar;68(3):216-25.
- Salama AA, Ismael NM, Bedewy M. The Anti-inflammatory and Antiatherogenic In Vivo Effects of Pomegranate Peel Powder: From Waste to Medicinal Food. J Med Food. 2021Feb;24(2):145-50.
- Aviram M, Rosenblat M. Pomegranate Protection against Cardiovascular Diseases. Evid Based Complement Alternat Med. 2012;2012:382763.
- Razani Z, Dastani M, Kazerani HR. Cardioprotective Effects of Pomegranate (Punica granatum) Juice in Patients with Ischemic Heart Disease. Phytother Res. 2017 Nov;31(11):1731-8.
- Sumner MD, Elliott-Eller M, Weidner G, et al. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart disease. Am J Cardiol. 2005 Sep 15;96(6):810-4.