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♡ Heart-Healthy Bioflavonoids ♡ - Part 2

Multiethnic Couple in the Kitchen Preparing Healthy Smoothie - InterPlexus Blog


In Part 2 of our American Heart Month blog series below, you will learn more about health conditions that affect your heart and the beneficial effects citrus bioflavonoids offer for your cardiovascular system.1,2

Review of Part 1

In Part 1, we learned that bioflavonoids, which are also known as flavonoids, are natural plant-based compounds that offer many health benefits. Research shows this diverse group of natural compounds have blood sugar-lowering, cholesterol-lowering, antioxidant, anticancer, kidney-protective, and liver-protective activities when consumed as part of a healthy diet.2 So far, more than 5000 different flavonoids have been discovered.3

While we could author an entire textbook about the health benefits of bioflavonoids, this blog will focus on citrus bioflavonoids and the benefits they provide to the cardiovascular system. The cardiovascular system includes your heart and blood vessels.

Fresh citrus fruits - InterPlexus Blog

The Cardiovascular Benefits of a Full-Spectrum Citrus Bioflavonoid Complex

Citrus fruits are an especially rich source of heart-healthy bioflavonoid compounds. The dietary flavonoids present in citrus fruits include hesperidin, hesperetin, naringin, naringenin, diosmin, quercetin, rutin, nobiletin, tangeretin, and many others. Common citrus fruits that contain these flavonoids include bergamots, grapefruits, lemons, limes, mandarins, oranges, and pomelos.2

Citrus flavonoids offer an impressive array of health-related benefits. In general, citrus flavonoids offer antioxidant, cell-protective, and anti-inflammatory properties. Since inflammation and oxidative stress play significant roles in the development of cardiovascular disease, it makes sense that an increased intake of citrus flavonoids could support a healthy cardiovascular system. Ample research confirms the intake of citrus flavonoids is associated with improved cardiovascular outcomes.2

Numerous studies show that citrus flavonoids prevent cardiovascular disease through multiple mechanisms and different pathways, including the inhibition of oxidative stress, optimization of platelet aggregation, reduced inflammation, improvement in lipid metabolism, regulation of cell death (apoptosis and autophagy), and modulation of the gut microbiome. For a summary of these actions, see the illustration below.4

The Role of Citrus Flavonoids - InterPlexus Blog

[Image from: Deng Y, Tu Y, Lao S, et al. The role and mechanism of citrus flavonoids in cardiovascular diseases prevention and treatment. Crit Rev Food Sci Nutr. 2022;62(27):7591-7614. doi:10.1080/10408398.2021.1915745] 

When healthy, the body maintains a dynamic and optimal balance between oxidation and anti-oxidation. Once this delicate balance is disrupted, reactive oxygen species (ROS) and reactive nitrogen are produced by oxidative stress and cause damage to your cells. Nearly all bioflavonoids offer antioxidant activity.4

Antioxidants are compounds that delay or inhibit the oxidation of molecules in the body; a high level of reactive oxygen species (ROS) is the major cause of cell death throughout the body.2 According to reports, flavonoids are the most powerful compounds that fight ROS and protect cells against oxidative stress. The antioxidant properties of citrus flavonoids allow them to inactivate ROS and scavenge free radicals to improve vascular endothelial inflammation and lipid levels and protect cardiovascular function.4

Family having breakfast at the weekend at kitchen

An abundance of epidemiological data indicates eating more fruits and vegetables reduces the risk of cardiovascular diseases. Moreover, when the consumption of citrus fruits or their juices is specifically analyzed, we also see a significant reduction in cardiovascular events.4

Cardiovascular diseases include atherosclerosis (hardening of the arteries), stroke, and other conditions. Several health concerns, such as hypertension (high blood pressure), hyperlipidemia (hypercholesterolemia), diabetes, and obesity, increase the risk of developing cardiovascular disease. The research explored below suggests citrus bioflavonoids significantly improve the health of those with diabetes, obesity, hypertension, atherosclerosis, stroke, and hyperlipidemia.2*

A glass of fresh orange juice and group of fresh orange fruits with green leaves - InterPlexus Blog

What is Atherosclerosis?

Atherosclerosis involves the abnormal deposition of fibrous tissue, cholesterol, and lipid plaques in the innermost layer of the large- and medium-sized arteries. Atherosclerosis is driven by chronic inflammation, and the plaques lead to the hardening and narrowing of the arteries.2

Atherosclerosis affects the basic structure of vessels and can result in the partial or complete blockage of arteries. When atherosclerosis affects the coronary arteries, it can cause ischemic heart failure and heart attacks. High cholesterol levels, hypertension, smoking, and diabetes all increase the risk of developing atherosclerosis.2

Genetic studies show drinking orange juice (500 mL per day) for four weeks affects the expression of 3,422 genes, including a large number of genes that play a role in inflammation and atherosclerosis. Participants in a clinical trial who drank 500 mL of red orange juice every day experienced significant improvements in the function of their vascular endothelial cells and levels of inflammation in the blood vessel walls.4

Fresh citruses and juice - InterPlexus Blog

A 90-day randomized, double-blind, placebo-controlled trial that included obese participants with an atherogenic index of plasma (AIP) of over 0.34 determined a citrus bioflavonoid complex reduced fasting glucose by 18.1%, triglycerides by 32%, and cholesterol parameters by up to 41.4%. The citrus bioflavonoid complex included neoeriocitrin, naringin, neohesperidin, melitidin, bruteridin, and other bioflavonoids.5

The AIP is an objective measurement of the unfavorable blood lipid profile that increases the risk of developing atherosclerosis. AIP values above 0.21 indicate a high risk of developing atherosclerosis and other cardiovascular diseases, while AIP values below 0.2 correlate with a low risk of developing atherosclerosis. Overall, the beneficial effects of the citrus bioflavonoid complex caused a powerful reduction in the AIP in the group that received the high dose of the bioflavonoids. The robust dose of the citrus bioflavonoid complex reduced the AIP to less than 0.2 in all participants to significantly decrease their risk of developing atherosclerosis.5

Beautiful lovely nice charming cheerful mom - InterPlexus Blog

What is Hypertension?

Hypertension is elevated blood pressure. It is the #1 contributing factor to all-cause global mortality and affects nearly 1.4 billion adults worldwide. Hypertension is the primary risk factor for ischemic stroke, hemorrhagic stroke, and coronary artery disease. Moreover, hypertension increases the risk of developing renal failure, heart failure, peripheral vascular disease, and many other medical conditions.6

Normal blood pressure is necessary for the healthy activity of the cardiovascular system and optimal blood flow. Citrus fruit flavonoids act as vessel relaxants and help maintain optimal vasculature tone. An animal study showed that taking hesperidin for eight weeks significantly reduced blood pressure, oxidative stress, endothelial dysfunction, and other cardiac and vascular abnormalities.2

A double-blind, cross-over study conducted at the Metabolic Unit at Kaplan Medical Center in Rehovot, Israel assessed the effects of sweetie fruit juice on subjects with stage I hypertension. Sweetie fruit is a hybrid between grapefruit and pummelo with a very high content of flavonoids, including naringin and narirutin.7

Sweetie fruit (green grapefruit, pomelit) - InterPlexus Blog

Participants alternately received high-flavonoid (HF) sweetie juice and low-flavonoid (LF) sweetie juice for five weeks. The HF juice reduced both the systolic and diastolic blood pressure (DBP), and the LF juice reduced the systolic blood pressure (SBP) in participants.7

A randomized, parallel, double-blind, placebo-controlled trial that included 159 hypertensive participants looked at the effects of a placebo, orange juice (OJ), or hesperidin-enriched orange juice (EOJ) on blood pressure and pulse pressure (PP), which is a measurement of arterial stiffness. The participants were divided into three groups that consumed 500 mL of juice daily for twelve weeks. The average reductions in SBP throughout the study were −6.35 and −7.36 mmHg for the OJ and EOJ interventions, respectively. Overall, the results illuminate a dose-dependent decrease in SBP and PP after sustained consumption of hesperidin. Chronic consumption of the EOJ also enhanced the acute postprandial decreases in SBP, DBP, and PP.8

Another clinical study that included patients with type 2 diabetes confirmed that consumption of 500 mg of hesperidin per day over six weeks led to decreases in SBP and DBP.8

Freshly cut orange fruit on a wooden cutting board - InterPlexus Blog

What is a Stroke?

Strokes are the fourth leading cause of death and the number one cause of long-term disability in the United States. Stroke is also a leading cause of death and long-term disability worldwide. Hypertension, smoking, hyperlipidemia, obesity, physical inactivity, diabetes, and alcohol intake are factors that increase the risk of stroke.9

Strokes can be either hemorrhagic or ischemic. Hemorrhagic strokes are less common and comprise about 20% of all strokes.10 A hemorrhagic stroke is caused by the rupture of a blood vessel, which leads to bleeding in the brain.11 An ischemic stroke is caused by either a blood clot or debris from elsewhere in the body blocking blood flow through the affected vessel.12

Platelets, which are also known as thrombocytes, play a crucial role in healthy blood clotting. However, excessive activation of platelets can contribute to several disorders, including high blood pressure and strokes. Platelet dysfunction is associated with the formation of blood clots and cardiovascular disease in general.2

Pretty woman holding glass with tasty juice - InterPlexus Blog

According to research, flavonoids reduce cell adhesion and improve the function of the vascular endothelium, which is the lining of the blood vessels. Epidemiological reports show the higher the consumption of citrus flavonoids, the lower the platelet activity. Therefore, citrus flavonoids can play a protective role against cardiovascular disease via their effect on platelets. Since flavonoids inhibit platelet function, they could be valuable anti-clotting agents to prevent ischemic stroke.2

A clinical trial concluded that drinking a glass of orange juice every day reduces the risk of stroke in men by 25%. Similarly, another clinical trial that included 14 years of follow-up in 69,622 female nurses concluded that ingesting large amounts of flavanones through orange and grapefruit juice reduces the risk of ischemic stroke by 19% in women.4

A large study with over 10,000 participants demonstrated an inverse association between daily citrus fruit intake and cardiovascular disease, specifically ischemic stroke. An inverse association means the more citrus fruits consumed, the lower the risk of stroke.2

Citrus fruits heart vitamin C on white background

What is Hyperlipidemia?

Hyperlipidemia is characterized by elevated or imbalanced lipid levels in the body. The lipids (fats) include total cholesterol, triglycerides, lipoproteins, chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), apolipoproteins, and high-density lipoprotein (HDL). Those with hyperlipidemia have approximately twice the risk of developing cardiovascular disease compared to those with normal cholesterol levels.13

A diet high in saturated or trans fats, physical inactivity, obesity, and smoking can increase the risk of developing hyperlipidemia. Several health conditions directly cause hyperlipidemia, including type 2 diabetes mellitus and hypothyroidism.13

Smiling little girl, eating her favorite food - InterPlexus Blog

In one clinical trial, participants with high cholesterol levels supplemented with 270 mg of citrus flavonoids and 30 mg of tocotrienols (Vitamin E) daily for four weeks. After four weeks of treatment, the participants experienced significant reductions in total cholesterol, LDL, and triglyceride levels. In patients with mildly elevated cholesterol levels, drinking 480 ml per day of orange juice for one year reduced total cholesterol, LDL, and apolipoprotein B (apoB) levels.2

Supplementation with 500 mg per day of glucosyl hesperidin for 24 weeks significantly reduced triglyceride and apoB levels in patients with elevated triglycerides. Another clinical study showed that the consumption of citrus fruit reduces the plasma level of triglycerides in patients with cardiovascular disease. A study that included participants with elevated cholesterol levels revealed that the intake of 400 mg of naringin daily for eight weeks reduced LDL and apoB levels in plasma by 17 percent.2

Happy senior couple cooking together in kitchen - InterPlexus Blog

Lipids (fats) are essential for many processes in the body. Dysregulation of lipid and lipoprotein (cholesterol) metabolism is one of the major contributing factors to the development of diabetes, cardiovascular disease, obesity, and inflammation. As noted above, several studies show citrus flavonoids modulate lipid metabolism and may prevent several diseases, including obesity and atherosclerosis.2*

Given the role of high blood sugar, abnormal platelet activity, hyperlipidemia, inflammation, and oxidative stress in the development of cardiovascular diseases, citrus flavonoids offer multi-layered protective benefits since they not only improve these conditions but also directly support the health of the heart and blood vessels, according to research.2,4*

Female hands giving red heart - InterPlexus Blog

Citrus flavonoids continue to be highly regarded by healthcare providers and researchers because they are naturally non-toxic (when consumed in recommended amounts) and offer impressive health-enhancing benefits.14*

Organic citrus bioflavonoids are available in Flavo PlexC, Adapt, and Zinc Plus.




* This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.



In honor of American Heart Month, we are sharing information about the beneficial effects of bioflavonoids on your cardiovascular system. Heart disease is the number one cause of death worldwide, so consider taking better care of your heart by reading our blogs and increasing your intake of heart-healthy bioflavonoids.*


Chronic stress is a frequent underlying cause of low nutrient levels and health issues. In fact, according to the World Health Organization (WHO), approximately 450 million people worldwide are affected by stress-related disorders. Research indicates stress could be responsible for an estimated 70% of visits to primary care providers, which is shocking. Fortunately, the consistent use of a synergistic blend of vitamins, minerals, and herbal extracts that nourish the adrenal glands could support a healthy stress response.*


The common cold is the most frequent human illness. Genetics, stress, smoking, nutrient deficiencies, and strenuous physical training can increase the risk of catching a cold. Modern research now confirms that supplemental vitamins, minerals, botanicals, and other natural remedies can decrease the severity and duration of the common cold.*


Summer is an opportune time to focus on health – the weather tends to be pleasant, which makes many people naturally feel like being more active and vigorous. Since June is also Men’s Health Month, let’s discuss a few nutrients that could be beneficial for men during a fun and healthy summer. According to the research, supplementing with zinc, vitamin C, and citrus bioflavonoids together could support optimal testosterone levels, recovery from injuries, and athletic performance.*



  1. U.S. commemorates 57th consecutive American Heart Month in February. Published November 14, 2022. Accessed December 2, 2022.
  2. Mahmoud AM, Hernández Bautista RJ, Sandhu MA, et al. Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health. Oxid Med Cell Longev. 2019;2019:5484138. doi:10.1155/2019/5484138
  3. Alappat B, Alappat J. Anthocyanin Pigments: Beyond Aesthetics. Molecules. 2020;25(23):5500. doi:10.3390/molecules25235500
  4. Deng Y, Tu Y, Lao S, et al. The role and mechanism of citrus flavonoids in cardiovascular diseases prevention and treatment. Crit Rev Food Sci Nutr. 2022;62(27):7591-7614. doi:10.1080/10408398.2021.1915745
  5. Capomolla AS, Janda E, Paone S, et al. Atherogenic Index Reduction and Weight Loss in Metabolic Syndrome Patients Treated with A Novel Pectin-Enriched Formulation of Bergamot Polyphenols. Nutrients. 2019;11(6):1271. doi:10.3390/nu11061271
  6. Manosroi W, Williams GH. Genetics of Human Primary Hypertension: Focus on Hormonal Mechanisms. Endocr Rev. 2019;40(3):825-856. doi:10.1210/er.2018-00071
  7. Reshef N, Hayari Y, Goren C, et al. Antihypertensive effect of sweetie fruit in patients with stage I hypertension. Am J Hypertens. 2005;18(10):1360-1363. doi:10.1016/j.amjhyper.2005.05.021
  8. Valls RM, Pedret A, Calderón-Pérez L, et al. Effects of hesperidin in orange juice on blood and pulse pressures in mildly hypertensive individuals: a randomized controlled trial (Citrus study). Eur J Nutr. 2021;60(3):1277-1288. doi:10.1007/s00394-020-02279-0
  9. Caprio FZ, Sorond FA. Cerebrovascular Disease: Primary and Secondary Stroke Prevention. Med Clin North Am. 2019;103(2):295-308. doi:10.1016/j.mcna.2018.10.001
  10. Montaño A, Hanley DF, Hemphill JC 3rd. Hemorrhagic stroke. Handb Clin Neurol. 2021;176:229-248. doi:10.1016/B978-0-444-64034-5.00019-5
  11. Unnithan AKA, M Das J, Mehta P. Hemorrhagic Stroke. In: StatPearls. Treasure Island (FL): StatPearls Publishing; September 30, 2022.
  12. Hui C, Tadi P, Patti L. Ischemic Stroke. In: StatPearls. Treasure Island (FL): StatPearls Publishing; June 2, 2022.
  13. Karr S. Epidemiology and management of hyperlipidemia. Am J Manag Care. 2017;23(9 Suppl):S139-S148.
  14. Ciumărnean L, Milaciu MV, Runcan O, et al. The Effects of Flavonoids in Cardiovascular Diseases. Molecules. 2020;25(18):4320. doi:10.3390/molecules25184320

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