The Pomegranate “Artery Cleaning” Clinical Trial

Published in Clinical Nutrition in 2004 and titled, “Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation,” Israeli researchers discovered pomegranate, administered in juice form over the course of a year, reversed plaque accumulation in the carotid arteries of patients with severe, though symptomless, carotid artery stenosis (defined as 70–90% blockage in the internal carotid arteries).

The study consisted of nineteen patients, 5 women and 14 men, aged 65-75, non-smokers. They were randomized to receive either pomegranate juice or placebo. Ten patients were in the pomegranate juice treatment group and 9 patients that did not consume pomegranate juice were in the control group. Both groups were matched with similar blood lipid and glucose concentrations, blood pressure, and with similar medication regimens which consisted of blood-pressure lowering (e.g. ACE inhibitors, β-blockers, or calcium channel blockers) and lipid lowering drugs (e.g. statins).

The ten patients in the treatment group group received 8.11 ounces (240 ml) of pomegranate juice per day, for a period of 1 year, and five out of them agreed to continue for up to 3 years.

The remarkable results were reported as follows:

“The mean intima media thickness the left and right common carotid arteries in severe carotid artery stenosis patients that consumed pomegranate juice for up to 1 year was reduced after 3, 6, 9 and 12 months of pomegranate juice consumption by 13%, 22%, 26% and 35%, respectively, in comparison to baseline values.”

You can only imagine what would happen if a pharmaceutical drug was shown to reverse plaque build up in the carotid arteries by 13% in just 3 months! This drug would be lauded the life-saving miracle drug, and not only would be promoted and sold successfully as a multi-billion dollar blockbuster, but discussion would inevitably follow as to why it should be mandated.

While these results are impressive, if not altogether groundbreaking for the field of cardiology, they may be even better than revealed in the stated therapeutic outcomes above.  When one factors in that the carotid artery stenosis increased 9% within 1 year in the control group, the pomegranate intervention group may have seen even better results than indicated by the measured regression in intima media thickness alone.  That is, if we assume that the pomegranate group had received no treatment, the thickening of their carotid arteries would have continued to progress like the control group at a rate of 9% a year, i.e. 18% within 2 years, 27% within 3 years. This could be interpreted to mean that after 3 years of pomegranate treatment, for instance, the thickening of the arteries would have been reduced over 60% beyond what would have occurred had the natural progression of the disease been allowed to continue unabated.  

3 Ways How Pomegranate Heals The Cardiovascular System

The researchers identified three likely mechanisms of action behind pomegranate’s observed anti-atherosclerotic activity:

• Antioxidant properties: Subjects receiving pomegranate saw significant reductions in oxidative stress, including decreases in autoantibodies formed against ox-LDL, a form of oxidized low density lipoprotein associated with the pathological process of atherosclerosis. Decreases in oxidative stress were measurable by an increase in the blood serum enzyme paraoxonase 1 (PON1) of up to 91% after 3 years; PON1 is an enzyme whose heightened activity is associated with lower oxidative stress. All of this is highly relevant to the question of pomegranate’s anti-atherosclerotic activity because of something called the lipid peroxidation hypothesis of atherosclerosis, which assumes that it is the quality of the blood lipids (i.e. whether they are oxidized/damaged or not), and not their quantity alone that determine their cardiotoxicity/atherogenicity. Essentially, pomegranate prevents the heart disease promoting effects of oxidative stress.
• Blood Pressure Lowering Properties: The intervention resulted in significant improvement in blood pressure: the patient’s systolic blood pressure was reduced 7%, 11% ,10%, 10% and 12% after 1, 3, 6, 9, and 12 months of pomegranate consumption, respectively, compared to values obtained before treatment. Pomegranate’s ability to reduce systolic blood pressure indicates it has a healing effect on the endothelium, or the inner lining of the artery which fails to relax fully in heart disease; a condition known as endothelial dysfunction.
• Plaque Lesion Stabilization: Because two of the ten patients on PJ (after 3 and 12 months) experienced clinical deterioration, carotid surgery was performed and the lesions were analyzed to determine the difference in their composition to those who did not receive pomegranate. The researchers noticed four distinct positive differences in the composition of the pomegranate-treated lesions: 1. Reduced Cholesterol Content: “The cholesterol content in carotid lesions from the two patients that consumed PJ was lower by 58% and 20%, respectively, in comparison to lesions obtained from CAS patients that did not consume PJ (Fig. 3A).” 2.     Reduced Lipid Peroxides: “[T]he lipid peroxides content in lesions obtained from the patients after PJ consumption for 3 or 12 months was significantly reduced by 61% or 44%, respectively, as compared to lesions from patients that did not consume PJ (Fig. 3B). 3.     Increased Reduced Glutathione Content: “A substantial increase in the lesion reduced glutathione (GSH) content, (GSH is a major cellular antioxidant) by 2.5-fold, was observed after PJ consumption for 3 or 12 months, (Fig. 3C). 4.     Reduced LDL Oxidation: “LDL oxidation by lesions derived from the patients after PJ consumption for 3 or 12 months, was significantly (Po0.01) decreased by 43% or 32%, respectively, in comparison to LDL oxidation rates obtained by lesions from CAS patients that did not consume PJ (Fig. 3D).”

Essentially these results reveal that not only does pomegranate reduce the lesion size in the carotid arteries, but “the lesion itself may be considered less atherogenic after PJ consumption, as its cholesterol and oxidized lipid content decreased, and since its ability to oxidize LDL was significantly reduced.”

This finding is quite revolutionary, as presently, the dangers of carotid artery stenosis are understood primarily through the lesion size and not by assessing for the quality of that lesion. This dovetails with the concept that the sheer quantity of lipoproteins (i.e. “cholesterol”) in the blood can not accurately reveal whether those lipoproteins are actually harmful (atherogenic); rather, if lipoproteins are oxidized (e.g. ox-LDL) they can be harmful (or representative of a more systemic bodily imbalance), whereas non-oxidized low density lipoprotein may be considered entirely benign, if not indispensable for cardiovascular and body wide health. Indeed, in this study the researchers found the pomegranate group had increased levels of triglycerides and very low density lipoprotein, again, underscoring that the anti-atherosclerotic properties likely have more to do with the improved quality of the physiological milieu within which all our lipoproteins operate than the number of them, in and of itself.

Finally, it should be pointed out that all the patients in this study were undergoing conventional, drug-based care for cardiovascular disease, e.g. cholesterol- and blood pressure-lowering agents. Not only did the pomegranate treatment not appear to interfere with their drugs, making it a suitable complementary/adjunct therapy for those on pharmaceuticals, but it should be pointed out that the control group’s condition got progressively worse (e.g. the mean IMT increased 9% within 1 year), speaking to just how ineffective drugs are, or how they may even contribute to the acceleration of the disease process itself.

Further Validation of Pomegranate’s Artery-Clearing Properties

Pomegranate’s value in cardiovascular health may be quiet broad, as evidenced by the following experimentally confirmed properties:

• Anti-inflammatory: Like many chronic degenerative diseases, inflammation plays a significant role in cardiovascular disease pathogenesis. There are five studies on GreenMedInfo.com indicating pomegranate’s anti-inflammatory properties.[iii]
• Blood-Pressure Lowering: Pomegranate juice has natural angiotensin converting enzyme inhibiting properties, [iv] and is a nitric oxide enhancer, two well-known pathways for reducing blood pressure. [v] Finally, pomegranate extract rich in punicalagin has been found reduce the adverse effects of perturbed stress on arterial segments exposed to disturbed flow.[vi]
• Anti-Infective: Plaque buildup in the arteries often involves secondary viral and bacterial infection, including hepatitis C and Chlamydia pneumoniae.[vii] Pomegranate has a broad range of anti-bacterial and anti-viral properties.
• Antioxidant: One of the ways in which blood lipids become heart disease-promoting (atherogenic) is through oxidation. LDL, for instance, may be technically ‘elevated’ but harmless as long as it does not readily oxidize. Pomegranate has been found to reduce the oxidative stress in the blood, as measured by serum paraoxonase levels.  One study in mice found this decrease in oxidative stress was associated with 44% reduction in the size of atherosclerotic lesions. [viii]
• Ant-Infective: While it is commonly overlooked, cardiovascular disease, and more particularly atherosclerosis, is connected to infection. Dentists know this, which is why they often prescribe antibiotics following dental work which releases bacteria into systemic circulation. Plaque in the arteries can also harbor viral pathogens. Pomegranate happens to have potent antiviral and antibacterial properties relevant to cardiovascular disease initiation and progression. It has been studied to combat the following infectious organisms:
  1. Avian Influenza
  2. Candida
  3. Escherichia Coli
  4. Hepatitis B
  5. HIV
  6. Influenza A
  7. Poxviruses
  8. Salmonella
  9. SARS
  10. Staphylococcus auerus
  11. Vaccinia virus
  12. Vibrio (Cholera) virus

For additional research on pomegranate’s heart friendly properties read our article: Research: Pomegranate May Reverse Blocked Arteries, and to learn more about it’s broadly therapeutic properties read: 100+ Health Properties of Pomegranate Now Includes Helping Diabetics.

Also, view our dedicated research section on reversing arterial plaque: Clogged Arteries

Resources

• [i] Aishah Al-Jarallah, Fatima Igdoura, Yi Zhang, Christine B Tenedero, Elizabeth J White, Melissa E Macdonald, Suleiman A Igdoura, Bernardo L Trigatti. The effect of pomegranate extract on coronary artery atherosclerosis in SR-BI/APOE double knockout mice.Atherosclerosis. 2013 May ;228(1):80-9. Epub 2013 Mar 7. PMID: 23528829

• [ii] Michael Aviram, Mira Rosenblat, Diana Gaitini, Samy Nitecki, Aaron Hoffman, Leslie Dornfeld, Nina Volkova, Dita Presser, Judith Attias, Harley Liker, Tony Hayek. 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. PMID: 15158307

• [iii] GreenMedInfo.com, Pomegranate’s Anti-Inflammatory Properties

• [iv] Mahalaxmi Mohan, Harshal Waghulde, Sanjay Kasture. Effect of pomegranate juice on Angiotensin II-induced hypertension in diabetic Wistar rats. Phytother Res. 2009 Dec 17. PMID: 20020514

• [v] Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P D’Armiento, Carmela Fiorito, Louis J Ignarro, Claudio Napoli. The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats. Nitric Oxide. 2007 Aug ;17(1):50-4. Epub 2007 May 5. PMID: 17553710

• [vi] Filomena de Nigris, Sharon Williams-Ignarro, Vincenzo Sica, Lilach O Lerman, Francesco P D’Armiento, Russell E Byrns, Amelia Casamassimi, Daniela Carpentiero, Concetta Schiano, Daigo Sumi, Carmela Fiorito, Louis J Ignarro, Claudio Napoli. Effects of a pomegranate fruit extract rich in punicalagin on oxidation-sensitive genes and eNOS activity at sites of perturbed shear stress and atherogenesis. Cardiovasc Res. 2007 Jan 15;73(2):414-23. Epub 2006 Sep 1. PMID: 17014835

• [vii] Yasunori Sawayama, Kyoko Okada, Shinji Maeda, Hachiro Ohnishi, Norihiro Furusyo, Jun Hayashi. Both hepatitis C virus and Chlamydia pneumoniae infection are related to the progression of carotid atherosclerosis in patients undergoing lipid lowering therapy. Fukuoka Igaku Zasshi. 2006 Aug;97(8):245-55. PMID: 17087362

• [viii] M Aviram, L Dornfeld, M Rosenblat, N Volkova, M Kaplan, R Coleman, T Hayek, D Presser, B Fuhrman. 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. PMID: 10799367