For many years, heart disease was thought of as a clogged pipe. That is, the more dietary fat you ate, the more would stick to your arteries and create a sticky plaque.
This story was, unfortunately, an oversimplification, popularized by the low-fat craze during the 80s and 90s. (2) Since then, clinical evidence has demonstrated how uncontrolled inflammation and oxidative stress are linked to the early progression of many cardiovascular and metabolic diseases, such as type 2 diabetes, hypertension, and atherosclerosis, now described as “cardiometabolic disease.” (7)(11)(23)
While uncontrolled oxidative stress is detrimental to health, not all oxidation is bad! In the right amount, free radicals called reactive oxygen species (ROS) actually help your body function properly by acting as signaling molecules. It’s only when our body’s natural antioxidant defense system cannot keep up that ROS and other oxidants become harmful. (28)

In the conventional approach of treating metabolic disease, the emphasis is to control cardiovascular risk with multiple drugs that improve common lab measurements, such as blood pressure, blood glucose, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total cholesterol.
While prescription drugs are certainly necessary for some patients, this approach has been unsuccessful in slowing the metabolic syndrome (METs) and obesity epidemic. (1) Given the relationship between uncontrolled oxidation and metabolic disease, strategies aimed at improving oxidative metabolism are becoming exciting additions to traditional therapies. (27)
The endothelium and oxidative vascular dysfunction
The endothelium is the one-cell-thick lining of blood vessels that acts as an interface for the blood and the rest of our body. Once thought of as a simple barrier, the endothelium is considered one of our largest organ systems, maintaining vascular tone through a variety of intricate mechanisms including nitric oxide (NO) production. (4)(13) Recognized as one of the most important molecules for vascular health, NO is the primary molecule that causes vascular relaxation, as well as being a protective antioxidant. (13)
Endothelial dysfunction (ED), now viewed as the earliest event of cardiometabolic diseases, occurs when NO levels fall to the point when your body is unable to properly dilate its blood vessels, which increases blood pressure. (13)(15) LDL particles in the bloodstream are also vulnerable to oxidative damage, becoming oxidized LDL (oxLDL), which are deposited in the artery wall and form fatty streaks and plaques. (15) High amounts of sugar in the blood react with proteins and lipids to form advanced glycation end products (AGEs), which increase ROS production and tissue damage, and are associated with diabetes and many age-related diseases. (12)
Foods for heart health and oxidation issues
Perhaps the most powerful way to balance inflammation and oxidative stress is through the foods you eat. As one of the most researched dietary patterns, the Mediterranean diet is commonly recommended for cardiovascular health. (24) Characterized by a high antioxidant and polyphenol concentration, clinical trials show that the Mediterranean diet was able to increase antioxidant levels in patients with high cardiovascular risk and significantly reduce heart attack, stroke, and death from CV outcomes over a 4.8-year follow-up compared with a low-fat diet. (3)
Supplements for heart health and oxidation issues
Several foods found in the Mediterranean diet have shown improvements in many cardiometabolic risk factors, prompting scientists to extract and concentrate these health-promoting molecules into researched, standardized supplements. Let’s explore how the following four supplements can help protect your endothelium, support the antioxidant defense system, and balance oxidative metabolism.
1. Bergamot
Citrus fruits are very high in antioxidant vitamin C, but they also contain numerous polyphenols that have many diverse mechanisms beneficial to cardiometabolic disease. Citrus flavonoids possess both anti-inflammatory and antioxidant abilities, as well as improve glucose tolerance and insulin sensitivity. (16)

One Mediterranean citrus fruit, known as bergamot, has a unique spectrum of polyphenols that not only lower inflammation and oxidative stress, but also naturally lower cholesterol production without side effects. (5)(18) Human clinical trials using bergamot extract show significant improvements in both lipid and glucose levels, making bergamot extract a powerful supplement for overall cardiometabolic health. (18)(21)
2. French maritime pine
During a French sea expedition in the 1500s, pine bark and needles were used as a tea to prevent scurvy. Since then, French maritime bark extract has been shown to contain not only vitamin C, but also powerful bioactive polyphenols called oligomeric procyanidins with strong antioxidant activity. (14) Clinical research shows this extract improves many aspects of cardiometabolic and vascular health, including lowering blood pressure and oxLDL levels, as well as increasing HDL, or “good” cholesterol. (25)
3. Pomegranate
Used as a symbol of fertility throughout history, pomegranates have long been viewed as possessing health-promoting properties. (19) Packed with potent antioxidant polyphenols called punicalagins, pomegranates and pomegranate extracts have been clinically studied to improve blood pressure and cholesterol levels, as well as improve endothelial function. (20)(22)(26)
4. Olives
As a staple of the Mediterranean diet, olives and olive oil have been investigated for their role in the diet’s beneficial effects. (6) And while olive oil is a rich source of healthy monounsaturated fatty acids (MUFAs), it also contains beneficial polyphenols shown to benefit many aspects of general health due to their anti-oxidant and anti-inflammatory activities. (6)(10)

Due to the low concentration of polyphenols found in many olive oils, standardized olive extracts were developed. (9)(20) Clinical trials examining standardized olive extract have shown reductions in markers of oxidative stress, inflammation, and increases in endothelial function. (20)
The bottom line
While the foundation for addressing any metabolic disease is a healthy diet, lifestyle practices, and exercise, specific polyphenol-rich foods and supplements are emerging as powerful tools to balance oxidation and support cardiometabolic health. Ask your healthcare practitioner which options are best for you before beginning a new treatment plan!
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Disclosure: This article was written in partnership with Ortho Molecular Products. All supplier partnerships have been approved by doctors on our Integrative Medical Advisory team, and this content adheres to all guidelines outlined in our content philosophy. Fullscript has not been compensated financially for the publication of this article.
- Adult Obesity Facts. (2018). Retrieved from Centers for Disease Control and Prevention website: https://www.cdc.gov/obesity/data/adult.html
- Berge, L., & F, A. (2008). How the Ideology of Low Fat Conquered America. Journal of the History of Medicine and Allied Sciences, 63(2), 139–177. https://doi.org/10.1093/jhmas/jrn001
- Billingsley, H. E., & Carbone, S. (2018). The antioxidant potential of the Mediterranean diet in patients at high cardiovascular risk: an in-depth review of the PREDIMED. Nutrition & Diabetes, 8(1). https://doi.org/10.1038/s41387-018-0025-1
- Brandes, R. P. (2014). Endothelial Dysfunction and Hypertension. Hypertension, 64(5), 924–928. https://doi.org/10.1161/hypertensionaha.114.03575
- C. Nauman, M., & J. Johnson, J. (2019). Clinical application of bergamot (Citrus bergamia) for reducing high cholesterol and cardiovascular disease markers. Integrative Food, Nutrition and Metabolism, 6(2). https://doi.org/10.15761/ifnm.1000249
- Castañer, O., Covas, M.-I., Khymenets, O., Nyyssonen, K., Konstantinidou, V., Zunft, H.-F., … Fitó, M. (2012). Protection of LDL from oxidation by olive oil polyphenols is associated with a downregulation of CD40-ligand expression and its downstream products in vivo in humans. The American Journal of Clinical Nutrition, 95(5), 1238–1244. https://doi.org/10.3945/ajcn.111.029207
- Cervantes Gracia, K., Llanas-Cornejo, D., & Husi, H. (2017). CVD and Oxidative Stress. Journal of Clinical Medicine, 6(2). https://doi.org/10.3390/jcm6020022
- Colica, C., Di Renzo, L., Trombetta, D., Smeriglio, A., Bernardini, S., Cioccoloni, G., … De Lorenzo, A. (2017). Antioxidant Effects of a Hydroxytyrosol-Based Pharmaceutical Formulation on Body Composition, Metabolic State, and Gene Expression: A Randomized Double-Blinded, Placebo-Controlled Crossover Trial. Oxidative Medicine and Cellular Longevity, 2017. https://doi.org/10.1155/2017/2473495
- Covas, M.-I., de la Torre, K., Farré-Albaladejo, M., Kaikkonen, J., Fitó, M., López-Sabater, C., … de la Torre, R. (2006). Postprandial LDL phenolic content and LDL oxidation are modulated by olive oil phenolic compounds in humans. Free Radical Biology and Medicine, 40(4), 608–616. https://doi.org/10.1016/j.freeradbiomed.2005.09.027
- de la Torre-Carbot, K., Chávez-Servín, J. L., Jaúregui, O., Castellote, A. I., Lamuela-Raventós, R. M., Nurmi, T., … López-Sabater, M. C. (2010). Elevated circulating LDL phenol levels in men who consumed virgin rather than refined olive oil are associated with less oxidation of plasma LDL. The Journal of Nutrition, 140(3), 501–508. https://doi.org/10.3945/jn.109.112912
- Dusting, G. J., & Triggle, C. (2005). Are We Over Oxidized? Oxidative Stress, Cardiovascular Disease, and the Future of Intervention Studies with Antioxidants. Vascular Health and Risk Management, 1(2), 93–97. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1993935/
- Gkogkolou, P., & Böhm, M. (2012). Advanced glycation end products. Dermato-Endocrinology, 4(3), 259–270. https://doi.org/10.4161/derm.22028
- Gradinaru, D., Borsa, C., Ionescu, C., & Prada, G. I. (2015). Oxidized LDL and NO synthesis—Biomarkers of endothelial dysfunction and ageing. Mechanisms of Ageing and Development, 151, 101–113. https://doi.org/10.1016/j.mad.2015.03.003
- Jean-Louis, A., & Yannick, P. (2007). PROCYANIDINS FROM FRENCH MARITIME PINE BARK Extraction and Biological Properties. NUTRAfoods.
- Leiva, E., Wehinger, S., Guzmán, L., & Orrego, R. (2015). Role of Oxidized LDL in Atherosclerosis. Hypercholesterolemia. https://doi.org/10.5772/59375
- Mahmoud, A. M., Hernández Bautista, R. J., Sandhu, M. A., & Hussein, O. E. (2019). Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health. Oxidative Medicine and Cellular Longevity, 2019, 1–19. https://doi.org/10.1155/2019/5484138
- Marrugat, J., Covas, M.-I., Fitó, M., Schröder, H., Miró-Casas, E., Gimeno, E., … Farré, M. (2004). Effects of differing phenolic content in dietary olive oils on lipids and LDL oxidation. European Journal of Nutrition, 43(3), 140–147. https://doi.org/10.1007/s00394-004-0452-8
- Perna, S., Spadaccini, D., Botteri, L., Girometta, C., Riva, A., Allegrini, P., … Rondanelli, M. (2019). Efficacy of bergamot: From anti‐inflammatory and anti‐oxidative mechanisms to clinical applications as preventive agent for cardiovascular morbidity, skin diseases, and mood alterations. Food Science & Nutrition, 7(2), 369–384. https://doi.org/10.1002/fsn3.903
- Pomegranate. (2014, November 17). Retrieved February 26, 2020, from NCCIH website: https://nccih.nih.gov/health/pomegranate/at-a-glance
- Quirós-Fernández, R., López-Plaza, B., Bermejo, L., Palma-Milla, S., & Gómez-Candela, C. (2019). Supplementation with Hydroxytyrosol and Punicalagin Improves Early Atherosclerosis Markers Involved in the Asymptomatic Phase of Atherosclerosis in the Adult Population: A Randomized, Placebo-Controlled, Crossover Trial. Nutrients, 11(3), 640. https://doi.org/10.3390/nu11030640
- Ross Walker, V. M. (2014). Bergamot Polyphenols: Pleiotropic Players in the Treatment of Metabolic Syndrome. Journal of Metabolic Syndrome, 03(02). https://doi.org/10.4172/2167-0943.1000143
- Stockton, A., Farhat, G., McDougall, G. J., & Al-Dujaili, E. A. S. (2017). Effect of pomegranate extract on blood pressure and anthropometry in adults: a double-blind placebo-controlled randomised clinical trial. Journal of Nutritional Science, 6. https://doi.org/10.1017/jns.2017.36
- Sverdlov, A. L., Figtree, G. A., Horowitz, J. D., & Ngo, D. T. M. (2016). Interplay between Oxidative Stress and Inflammation in Cardiometabolic Syndrome. Mediators of Inflammation, 2016, 1–3. https://doi.org/10.1155/2016/8254590
- Tuttolomondo, A., Simonetta, I., Daidone, M., Mogavero, A., Ortello, A., & Pinto, A. (2019). Metabolic and Vascular Effect of the Mediterranean Diet. International Journal of Molecular Sciences, 20(19). https://doi.org/10.3390/ijms20194716
- Valls, R.-M., Llauradó, E., Fernández-Castillejo, S., Puiggrós, F., Solà, R., Arola, L., & Pedret, A. (2016). Effects of low molecular weight procyanidin rich extract from french maritime pine bark on cardiovascular disease risk factors in stage-1 hypertensive subjects: Randomized, double-blind, crossover, placebo-controlled intervention trial. Phytomedicine, 23(12), 1451–1461. https://doi.org/10.1016/j.phymed.2016.08.007
- Vilahur, G., Padró, T., Casaní, L., Mendieta, G., López, J. A., Streitenberger, S., & Badimon, L. (2015). Polyphenol-enriched diet prevents coronary endothelial dysfunction by activating the Akt/eNOS pathway. Revista Espanola De Cardiologia (English Ed.), 68(3), 216–225. https://doi.org/10.1016/j.rec.2014.04.021
- Vona, R., Gambardella, L., Cittadini, C., Straface, E., & Pietraforte, D. (2019). Biomarkers of Oxidative Stress in Metabolic Syndrome and Associated Diseases. Oxidative Medicine and Cellular Longevity, 2019, 1–19. https://doi.org/10.1155/2019/8267234
- Zhang, J., Wang, X., Vikash, V., Ye, Q., Wu, D., Liu, Y., & Dong, W. (2016). ROS and ROS-Mediated Cellular Signaling. Retrieved February 26, 2020, from Oxidative Medicine and Cellular Longevity website: https://www.hindawi.com/journals/omcl/2016/4350965/