Oxidative Stress and Cardiovascular Health

Oxidative stress may sound familiar. It is often mentioned in relation to free-radical-fighting antioxidants in food, cosmetics, and nutraceuticals. In fact, oxidative stress is an imbalance between antioxidants and free radicals, in which an overabundance of free radicals and insufficient antioxidants harm the body’s cells.¹ Free radicals are highly reactive molecules characterized by an unpaired electron that can be generated through endogenous processes like mitochondrial respiration as well as exogenous sources such as pollution. They are essential for some physiological processes, including cell signaling and immune defense, but overproduction is problematic.² Oxidative stress is linked to a host of chronic conditions, but let’s focus on its impact on cardiovascular health.

“Oxidative stress is a key driver of cardiovascular dysfunction,” says Irfan Qureshi, ND, global head of product development at Metagenics (Aliso Viejo, CA). “It accelerates cardiovascular disorders by overwhelming the body’s antioxidant defenses and its ability to fight free radicals. This contributes to poor vascular health and specifically to endothelial dysfunction. It also leads to the oxidation of cholesterol molecules, which can lead to plaque formation.”

“Excess ROS [Reactive Oxygen Species] initiates and amplifies vascular injury by oxidizing LDL cholesterol, promoting endothelial dysfunction, lipid retention, and progressive plaque formation that underlies atherosclerosis,” explains Stacey Smith, senior medical affairs liaison with Gnosis by Lesaffre (Milwaukee, WI). “In parallel, ROS impair vascular tone and nitric oxide signaling, increase vascular smooth muscle contractility, and drive hypertension and arterial stiffening.”

ROS are oxygen-containing free radicals. Both Qureshi and Smith note that oxidative stress also causes inflammation, further increasing risk for high blood pressure, heart attacks, and strokes. “Uncontrolled inflammatory processes can further lead to poor heart function and damage to the heart muscle itself,” says Qureshi.

“ROS activate NF-κB–dependent inflammatory pathways, stimulating the release of cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-β (TNF-β), which promote endothelial activation, leukocyte adhesion, and immune-driven plaque progression,” explains Smith. “High-sensitivity C-reactive protein (hs-CRP) and oxidized LDL reflect the systemic inflammatory burden. Within the myocardium, excessive oxidative stress induces cardiomyocyte apoptosis and necrosis, disrupts intracellular calcium handling, and triggers maladaptive remodeling, all leading to heart failure.”

With this in mind, what lifestyle and nutraceutical approaches help reduce oxidative stress?

“Research indicates that healthy lifestyle choices can help combat cardiovascular oxidative stress,” says Qureshi. “In terms of supplement ingredients that can help neutralize the damage associated with free radicals and potentially reduce heart disease risk, generally the goal should be to look for interventions that improve endothelial function, reduce inflammation, and support mitochondrial health.”

Nutraceutical Approaches

Some of the most popular cardiovascular health ingredients on the market have been demonstrated to reduce oxidative stress to support endothelial function. Among the most well-known antioxidant ingredients for cardiovascular health is Coenzyme Q10 (CoQ10).³ “CoQ10 is an indispensable nutrient for heart and vascular health as it supports mitochondrial health and function while playing a key role in the production of cellular energy via the production of ATP,” says Qureshi. “Heart muscle has a high demand for energy and Coenzyme Q10 supports cellular energy production to keep it pumping.”

CoQ10 is also available in a reduced form called ubiquinol, which studies has shown to ameliorate dyslipidemia-related endothelial dysfunction by increasing nitric oxide bioavailability and enhanced LDL antioxidant protection.⁴

Speaking of nitric oxide, beetroot and beetroot extracts “provide a key source of nitrates to help support nitric oxide production in the vascular endothelium,” says Qureshi. He goes on to explain that “Healthy nitric oxide levels promote the ability of blood vessels to relax (vasodilation) and help regulate healthy blood pressure and blood flow. Nitric oxide also has an anti-inflammatory effect in vascular tissue, and prevents platelet aggregation (thereby reducing the risk of forming clots).”⁵

Omega-3s, probably the most well-recognized and trusted ingredient class in the cardiovascular health category, are well known to support a healthy inflammatory response. “Omega-3s decrease the effects of inflammation on vascular tissue, support healthy lipid profiles, and improve endothelial health,” explains Qureshi. In vitro research also shows that EPA an DHA omega-3s attenuate oxidative stress-induced DNA damage in vascular endothelial cells.⁶

Nattokinase may also be a great option for supporting endothelial health, which Vincent Hackel, CEO and president of JBSL-USA (Walnut Creek, CA), says “offers heart benefits by breaking down blood clots (fibrinolysis), improving circulation, lowering blood pressure, and potentially reducing plaque, thus lowering risks for heart attack and stroke.”⁷

Nattokinase is derived from natto, which are fermented soybeans, and research indicates it may help “dissolve fibrin, thin blood, reduce blood viscosity, and may decrease triglycerides and cholesterol, supporting overall cardiovascular health,” Hackel explains.

Some research even indicates that nattokinase may elicit anti-inflammatory and anti-oxidative stress effects in addition to its thrombolytic and anticoagulant functions. These are, of course, connected functions, as inflammation and oxidative stress help promote thrombosis.⁸

Formulators should also consider certain vitamins and minerals, as they play a central role in fighting oxidative stress and supporting cardiovascular health. “No discussion about cardiovascular support would be complete without mentioning the key protective roles of magnesium, vitamin K₂ (particularly menaquinone-7), and vitamin D₃,” says Qureshi. “Magnesium reduces oxidative stress and supports the relaxation of endothelial tissue. It also activates vitamin D₃, which plays a crucial regulatory role in inflammation, endothelial function and calcium absorption. Low vitamin D levels are associated with increased inflammation, increased oxidative stress, and increased vascular dysfunction.”

When it comes to vitamin K₂, Qureshi explains that it “activates a protein known as matrix Gla protein, which is an inhibitor of vascular calcification, and supports optimal calcium transport, pushing calcium into bones and tissues where it should be and out of the vascular endothelium. This can help keep blood vessels supple and open, supporting healthy blood flow.”

Elaborating on the benefits of vitamin K₂, Smith says that experimental studies indicate that it reduces intracellular oxidative stress in vascular smooth muscle cells even in conditions with warfarin exposure where oxidative stress is induced by impairment of the vitamin K pathway. “This attenuation of oxidative stress has been accompanied by a reduced release of extracellular vesicles involved in calcification processes,” she explains. “In addition, vitamin K₂ has been linked to improved mitochondrial function, reflected by increased cellular ATP production, which may enhance cellular resistance to oxidative injury.”^{9, 10}

Smith also points out that human research has shown that there is a relationship between vitamin K status and oxidative stress in patients with chronic kidney disease, where “elevated dp-ucMGP (inactive MGP)—a marker of functional vitamin K deficiency—has been independently associated with malondialdehyde (MDA), a marker of lipid peroxidation.”¹¹

“Together, these findings suggest that insufficient vitamin K availability may be accompanied by a greater oxidative stress burden, potentially contributing to progressive vascular damage as kidney function declines,” she explains. “Taking this into consideration, these findings also suggest that vitamin K₂, particularly MK-7, may contribute to cardiovascular protection not only by regulating vascular calcification but also by modulating oxidative stress and mitochondrial function, thereby limiting oxidative vascular injury.”

Oxidative stress is an antecedent to a range of cardiovascular disease risk factors, and research indicates that many notable ingredients marketed for cardiovascular health exert anti-oxidative stress benefits. This offers brands an additional way to position well-established ingredients and to optimize cardiovascular health formulations to target oxidative stress as a pathway.

References

1. Cleveland Clinic. Oxidative stress. Accessed March 5, 2026. https://my.clevelandclinic.org/health/articles/oxidative-stress
2. Chandimali N, Bak SG, Park EH, et al. Free radicals and their impact on health and antioxidant defenses: a review. Cell Death Discov. 2025;11:19. doi:10.1038/s41420-024-02278-8.​
3. Gutierrez-Mariscal FM, Arenas-de Larriva AP, Limia-Perez L, et al. Coenzyme Q10 supplementation for the reduction of oxidative stress: clinical implications in the treatment of chronic diseases. Int J Mol Sci. 2020;21(21):7870. doi:10.3390/ijms21217870.
4. Sabbatinelli J, Orlando P, Galeazzi R, et al. Ubiquinol ameliorates endothelial dysfunction in subjects with mild-to-moderate dyslipidemia: a randomized clinical trial. Nutrients. 2020;12(4):1098. doi:10.3390/nu12041098.
5. Clifford T, Howatson G, West DJ, Stevenson EJ. The potential benefits of red beetroot supplementation in health and disease. Nutrients. 2015;7(4):2801-2822. doi:10.3390/nu7042801.
6. Sakai C, Ishida M, Ohba H, et al. Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells. PLoS One. 2017;12(11):e0187934. doi:10.1371/journal.pone.0187934.
7. Kurosawa Y, Nirengi S, Homma T, et al. A single dose of oral nattokinase potentiates thrombolysis and anticoagulation profiles. Sci Rep. 2015;5:11601. doi:10.1038/srep11601
8. Wu H, Wang Y, Zhang Y, et al. Breaking the vicious loop between inflammation, oxidative stress and coagulation: a novel antithrombus insight of nattokinase by inhibiting LPS-induced inflammation and oxidative stress. Redox Biol. 2020;32:101500. doi:10.1016/j.redox.2020.101500.
9. Petsophonsakul P, Furmanik M, Mees B, Schurgers L. Vitamin K ameliorates nicotine-induced calcification of VSMCs by inhibiting oxidative stress and extracellular vesicle secretion. Atherosclerosis. 2019;287:e258. Available at: https://www.atherosclerosis-journal.com/article/S0021-9150(19)31253-5/fulltext.[1]
10. Akbulut AC, Schurgers LJ. Non-canonical role of MK-7 in vascular smooth muscle cells: promoting energy and inhibiting oxidative stress. In: Proceedings of the 2nd International Electronic Conference on Nutrients; March 15-31, 2022; Basel, Switzerland. MDPI; 2022. doi:10.3390/IECN2022-12401
11. Neofytou I, Stamou A, Kontogiorgos I, Tsinari A. The association of dephosphorylated, uncarboxylated Matrix Gla Protein with vascular calcification and oxidative stress in chronic kindey disease patients. Nephronology Dialysis Transplantation. 2024; 40(Supplement 3). doi: 10.1093/ndt/gfaf116.0430