The excellent research team at Protocol for Life Balance comes through again with a comprehensive article detailing everything you need to know about cardiovascular supplements. Pay particular attention to the science behind nattokinase, one of the less well known but highly effective nutrients for circulatory health. There’s more to cardio prevention than just taking a statin!
—Dr. Ronald Hoffman
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The importance of maintaining a healthy cardiovascular system is not new; for decades, research has shown that not smoking and following a healthy lifestyle with a diet rich in vegetables (fiber), lean proteins, and healthy fats, as well as exercising regularly, contribute to maintaining cardiovascular health. As of 2026, have we made any progress in the United States? According to the CDC, only 36 % of U.S. adults have no cardiovascular disease risk factors.1 The American Heart Association tracks indicators of cardiovascular health with the “Life’s Essential 8” which are: not-smoking, physical activity, healthy diet, healthy body weight, sleep health, and control of cholesterol, blood pressure, and blood sugar. Some progress has been observed, with, for example, nearly 90% of adults not smoking. However, some areas for improvement remain since only 25% of adults meet the 2018 Physical Activity Guidelines for Americans for aerobic and muscle-strengthening activities. Being overweight, failing to maintain healthy cholesterol and glucose levels, and having abnormal blood pressure are also areas of concern.2 Overall, progress toward improving Americans’ cardiovascular health remains a challenge and is unlikely to improve significantly as the population ages.3 Alongside a healthy lifestyle, dietary supplements can really make a difference.
Nattokinase is a bioavailable fibrinolytic enzyme isolated from natto, a traditional Japanese fermented soy food that supports cardiovascular health by helping to maintain normal blood fluidity.* In vitro studies have demonstrated its ability to dissolve fibrin, an important factor involved in coagulation.* In laboratory experiments, the addition of nattokinase to whole human blood resulted in a dose-dependent decrease of red blood cell aggregation and blood viscosity.* A 2-month open-label, clinical trial with 45 subjects investigating the effect of taking a daily dose of 2 capsules of nattokinase [2,000 fibrinolysis units (FU) per capsule] revealed a significant reduction in plasma levels of fibrinogen (by 9%), and of coagulation factors VII (by 14%) and VIII (by 17%).4* Furthermore, in a randomized, double-blind, placebo-controlled trial, 86 participants receiving nattokinase (2,000 FU/capsule) for 8 weeks, researchers observed a significant reduction in blood pressure already within the normal range.5* Higher doses of nattokinase have been evaluated; in a clinical study, volunteers receiving 6,000 FU had significantly improved arterial thickness and maintained normal lipid levels already within the normal range.6* Furthermore, in a population study, a high daily nattokinase dose (10,800 FU) for up to 12 months maintained normal lipid levels already within the normal range.7,8*
Ubiquinol and CoQ10 share the same biological properties; ubiquinol is the reduced active form of CoQ10. At the molecular level, the ability of ubiquinol/CoQ10 to exchange electrons is central to cellular energy production.* Its powerful free radical neutralizing activity is also important for the protection of biological membranes against oxidative stress, as well as for regenerating antioxidants such as vitamin C and E.*
Scientific studies indicate that ubiquinol, which has superior bioavailability compared to other forms of CoQ10, can help support normal cardiovascular function.* Indeed, in a randomized, double-blind, single-center trial with 51 individuals receiving 100 mg or 200 mg ubiquinol daily, the authors observed that ubiquinol significantly improved endothelial function as measured by flow-mediated dilation of the brachial artery.9*
CoQ10 is also regularly used in dietary supplements aiming to support cardiovascular health.* However, CoQ10 is relatively poorly absorbed by the gastrointestinal tract. This issue can be partially resolved by taking CoQ10 with a fat-containing meal.10Furthermore, in clinical studies, oral doses as low as 60 mg/day resulted in concentrations above baseline and improvements in certain hemodynamic parameters.11*
Vitamins D and K are both fat-soluble vitamins that play central roles in calcium metabolism.* Vitamin D intake promotes the production of proteins that require activation by vitamin K in order to function properly.1*
Vitamin K2 is important for cardiovascular health.* Prospective observational studies have shown that higher intakes of dietary vitamin K2 are associated with healthier cardiovascular systems.* Randomized clinical trials have shown that menaquinone-7 (MK-7) supplementation (up to 360 mcg daily) results in significant improvement in markers of arterial stiffness.12-14*
Among ingredients found in cardiovascular-supporting supplements, vitamin D3 is often added as a synergistic agent with vitamin K2.* Preclinical research suggests that vitamin D may help regulate blood pressure via the renin-angiotensin-aldosterone system, support insulin metabolism, and directly impact vascular tissue.* It has been hypothesized that these proposed functions of vitamin D could explain the observed correlation between vitamin D deficiency and cardiovascular risk.15*
Furthermore, vitamins D and K are interrelated through the regulation of proteins that are involved in vascular calcification.* While it is not fully understood how vitamins D and K affect cardiovascular health at the cellular level, observational population studies have indicated that the combination of low serum vitamin D and low serum vitamin K was associated with higher systolic and diastolic blood pressure (while remaining within normal range).* This observation gives a valuable insight on how both vitamin D and K could be involved in cardiovascular health. 16*
In an interventional study investigating the combined effect of vitamins D and K on vascular function and calcification in healthy post-menopausal women, after 3 years of supplementation with 1000 μg/d vitamin K1 + 320 IU vitamin D, the vitamin D+K group maintained vessel wall characteristics of a healthy carotid artery, whereas the control group and the vitamin D-only group did not show any positive effect on the structure of carotid arteries.* These few studies show some potential for the combined effect of vitamins D and K versus vitamin D alone. However, it should be noted that, so far, very few clinical studies have been conducted in this field and that there is still a lot to discover – most notably, what is the optimal vitamin D to K ratio, and what is the best form of vitamin K to be used to achieve the cardiovascular benefits of combined vitamin D and K supplementation?17*
Other health benefits of vitamin D and K supplementation are under investigation, especially regarding their combined effects on insulin metabolism, endocrine function, and oxidative stress.17*
Current evidence suggests that joint supplementation with vitamins D and K may be more effective than either alone for cardiovascular health.* As more is discovered about the powerful combination of vitamins D and K, it gives a renewed reason to supplement your diet with both vitamin D3 and K2 alongside a healthy diet including a variety of foods such as vegetables and fermented dairy for bone and cardiovascular health. 17*
Carnitine is a nutrient often found in cardiovascular-supporting supplements.* It has been chosen for its ability to support energy production.* It facilitates the transport of fatty acids across the inner mitochondrial membrane for subsequent β‐oxidation, a process also known as the “carnitine shuttle.”* Fatty acids are the predominant substrate for energy production in skeletal and cardiac muscles.* In a double‐blind, randomized clinical trial with 14 healthy adult volunteers, 24 weeks of supplementation with L‐carnitine tartrate (Carnipure™, 2 g twice daily with 80 g of simple carbohydrates per intake) resulted in a significant increase in the total muscle carnitine content (21% as compared to baseline confirmed by biopsy), while it remained unchanged in the control group (80 g of carbohydrates twice daily).* When subjected to a standardized cycling exercise challenge, the carnitine group increased work output by 11% while the control group showed no change.* Additionally, the carnitine group utilized 55% less muscle glycogen (P < 0.05) during the challenge, which is consistent with an increase in lipid utilization for energy production.*
In addition to vitamins and nutrients, botanicals such as hawthorn and grape seed extract are commonly used in cardiovascular-supporting supplements.*
Hawthorn has a long traditional use in herbalism. Its extract has free radical-scavenging and cardioprotective properties.* It regulates coronary blood flow and enhances oxygen flow and utilization by the heart.* Hawthorn is known for its ability to enhance heart contraction, and it has vasodilatory properties.*
Grape seed extract possesses naturally occurring polyphenols that have been shown to neutralize free radicals. Numerous studies have demonstrated its positive effects on cardiovascular health.* However, not all grape seed extracts are created equal. MegaNatural®‐BP™ is a grapeseed extract standardized to a minimum of 90% polyphenols. This proprietary grape seed extract has been extensively investigated in laboratory settings and in randomized clinical studies. Results from these investigations show that MegaNatural®‐BP™ has powerful free radical scavenging properties and can contribute to endothelial relaxation in laboratory settings.* It may also affect platelet aggregation.* In a randomized, placebo-controlled clinical trial in 24 adult volunteers receiving 150 mg or 300 mg grape seed extract daily for four weeks, healthy blood pressure was significantly lowered in the grape seed group after four weeks versus baseline.*
As described above, MK-7, ubiquinol, MegaNatural®‐BP™ grape seed extract, and L-carnitine are clinically evaluated compounds working at different levels of the structure and function of blood vessels and the heart and cardiovascular system.*
Protocol For Life Balance® offers a wide range of cardiovascular-supporting supplements containing the ingredients described above, including Nattokinase and Ubiquinol (100 mg and 200 mg per softgel). Protocol For Life Balance® has also combined some of these ingredients in botanical-nutrient blends, such as in Clinical Cardio-6. With its extensive line of cardiovascular products, Protocol For Life Balance® allows you to tailor your supplementation program to your unique cardiovascular health needs.*
References:
1. https://www.cdc.gov/nchs/products/databriefs/db540.htm#Key_finding.
4. Hsia C-H, Shen M-C, Lin J-S, et al. Nutrition Research. 2009;29(3):190–196.
5. Kim JY, Gum SN, Paik JK, et al. Hypertension research : official journal of the Japanese Society of Hypertension. 2008;31(8):1583–1588.
6. Ren NN, Chen HJ, Li Y, McGowan GW, Lin YG. Zhonghua Yi Xue Za Zhi. 2017;97(26):2038–2042.
7. Chen H, Chen J, Zhang F, et al. Front Cardiovasc Med. 2022;9:964977.
8. Li X, Long J, Gao Q, et al. Rev Cardiovasc Med. 2023;24(8):234.
9. Sabbatinelli J, Orlando P, Galeazzi R, et al. Nutrients. 2020;12(4):1098.
10. Bhagavan HN, Chopra RK. Free Radic Res. 2006;40(5):445–453.
11. Jones K, Hughes K, Mischley L, McKenna DJ. Alternative therapies in health and medicine. 2004;10(1):22–30; quiz 31.
12. Knapen MH, Braam LA, Drummen NE, Bekers O, Hoeks AP, Vermeer C. Thromb Haemost. 2015;113(5).
13. Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JWJ. Atherosclerosis.225(2):397–402.
14. Haugsgjerd TR, Egeland GM, Nygård OK, et al. BMJ Open. 2020;10(5):e035953.
15. Judd SE, Tangpricha V. Am J Med Sci. 2009;338(1):40–44.
16. Mayer O, Jr., Seidlerova J, Wohlfahrt P, et al. J Nutr Biochem. 2017;46:83–89.
17. van Ballegooijen AJ, Pilz S, Tomaschitz A, Grübler MR, Verheyen N. International Journal of Endocrinology. 2017;2017.
* These statements have not been evaluated by the Food and Drug Administration. These products are not intended to diagnose, treat, cure, or prevent any disease.
