Natural Health: Quercetin and Heart Disease

Quercetin and quinoa may be tied for the two toughest words to pronounce in the health world. Unlike quinoa, which is a food, quercetin is found in foods but is not a food itself. It can be pronounced either as “quer-sit-in” or “quer-see-tin”. Focusing on a quercetin rich diet or supplementation may support healthy cardiovascular function and outcomes.

What is Quercetin?

Quercetin is a phytonutrient or plant derived chemical that falls in the family of polyphenol flavonoids. It further can be classified in a sub-category of flavonoids called flavanols. Humans cannot make quercetin as it has to be derived from plants. Many fruits, vegetables, and drinks contain it. It is found throughout nature and its name is derived from oak forest (quercetum), after the oak genus Quercus. Ingested alone it has a bitter flavor like many phytonutrients.

Where is Quercetin found in foods?

Quercetin is found in many plant foods including fruits, vegetables, seeds, grains and leaves. It is particularly abundant in onions and kale. In red onions it is more concentrated in the outer rings and closest to the root. Organic tomatoes may have significantly more quercetin than conventional tomatoes.  Additional foods that concentrate quercetin include grapes and red wine, berries, cherries, apples, citrus, buckwheat, broccoli, and black tea. It is also found in some herbs like gingko biloba. A ranking of the concentration of quercetin in plant foods is available (1).

What does quercetin do?

Quercetin has two principal activities that may support cardiovascular health, antioxidant properties and anti-inflammatory properties. Oxidative stress is a fundamental trigger of atherosclerosis and may arise from air pollution, smoking, chemical exposures, radiation and other factors. The free radicals created are unstable and may  cause damage to tissues leading to disease and accelerated aging. Quercetin is a powerful antioxidant and may be more powerful than the commonly known vitamins C, E and beta-carotene.

            Inflammation can be a helpful response to insult and injury if brief and it resolves. Chronic inflammation can be harmful to blood vessels and other cardiovascular structures. Common causes of chronic inflammation are poor quality diets rich in processed foods, excess processed meats, excess sugar, obesity, poor dental health, chronic infections, sleep apnea, and biotoxicity from heavy metals and other agents. Quercetin may reduce inflammation and studies in animal models and humans support this benefit.

Research on Quercetin and the Cardiovascular System

 1) Quercetin and Endothelial Function

There are an estimated 50,000 miles of arteries in the body supplying all tissues with highly oxygenated blood and nutrients. The inner lining of all arteries is composed of a single layer of cells that actively protect arteries from harm. This layer is called the endothelium. The endothelium is not only a barrier between any toxins in the blood and the rest of the arterial wall, endothelial cells can produce active compounds like nitric oxide and endothelin that can either dilate arteries to improve blood flow or the opposite. A normally functioning endothelial layer also resists atherosclerosis, inflammation and thrombosis. The impact of quercetin on endothelial function has been studied several times.

            In a randomized, controlled, crossover study, 25 participants with at least once risk factor for cardiovascular disease were given a modified quercetin or placebo. Measurements of endothelial function were made at baseline and 1.5 hours after the intervention. There was significantly better endothelial function after quercetin compared to the placebo. There was no change in blood pressure during this short study (2).

2) Quercetin and Blood Pressure

Chronically elevated blood pressure, known as hypertension, is the number one cause of death worldwide. Strategies for the prevention, and reversal of hypertension are of key importance. Many patients ask about natural therapies of hypertension. Quercetin has been studied in terms of its impact on blood pressure measurements.

            In randomized study of 70 subjects that were overweight or obese with early hypertension, a 6 week-long treatment with a quercetin rich powder or placebo was tested in a double-blinded protocol. In the subgroup with hypertension quercetin significantly reduced both day and night-time systolic blood pressures (3) .

In a cohort of 84 male patients with gout and hypertension, 43 patients were treated with quercetin and 41 acted as a comparison group.

84 male patients with gout and EH. The main groups consisted of 43 patients who were treated with quercetin for 12 months and a comparative group of 41 patients who were performed treatment without quercetin. At the end of a year, cardiac diastolic function was better than the control group and the mass of the left ventricle was also better. The blood pressure, both systolic and diastolic, were lower in the men treated with quercetin (4).

3) Quercetin and Nitric Oxide Production

One of the most important functions of healthy arteries and healthy endothelial function is the production of abundant nitric oxide, a vasodilator, and lesser amounts of endothelin, a vasoconstrictor. In a randomized study of 12 healthy men, quercetin (200 mg) was administered orally with or without a green tea extract. The green tea extract did not prove to alter nitric oxide production. Both quercetin and the green tea extract resulted in a reduction in plasma endothelin concentrations and only quercetin decreased urinary endothelin levels. Quercetin did increase measures of nitric oxide production (5).

4) Quercetin and Cholesterol Levels

Chronically elevated serum cholesterol levels, particularly the low-density lipoprotein or LDL-cholesterol, is a risk factor for developing atherosclerosis and clinic heart attacks, strokes, and premature death. Natural therapies of elevated cholesterol are often preferred by patients. In randomized study over 2 months, 200 healthy persons were randomized in a double-blind study of quercetin or placebo. After 2 months there was no change in the placebo group. In the quercetin arm there were significant decrease in total cholesterol, triglycerides, and LDL-cholesterol. Total cholesterol was reduced by over 40 mg/dl (6).

5) Quercetin and Advanced Glycation End Products (AGE)

Advanced glycation end products (AGEs) are a family of compounds created by modified proteins and lipids by a process of  “sugar coating”. AGEs form in excess in patients with chronically high blood sugars. AGEs are also formed by methods of cooking, particulary dry grilling of meats including poultry. Elevated production of AGEs may contribute to diseases of aging such as diabetes, dementia and cardiovascular disease. Strategies to prevent or lower AGEs production by diet, food preparation, and supplements are promising goals for optimal health.

            A cohort of 37 healthy adults with elevated blood pressure were included in a randomized, double-blind, placebo-controlled crossover trial involving and arm receiving 160 mg/day of quercetin for 4 weeks. Measurements of MGO, a marker of AGE production, were performed. Quercetin led to a reduction of MGO levels (7).

6) Quercetin and Visceral Adipose Tissue

Recent statistics indicate that up to 75% of Americans can be classified as overweight or obese. The pattern of excess fat distribution matters. Accumulation of fat around the waist on internal organs, referred to as visceral adipose tissue (VAT) is particularly adverse for inflammation and chronic disease development.

            To study the impact of quercetin on VAT levels, 70 healthy subjects that were of normal or overweight body composition entered a randomized, double-blind, placebo-controlled study over 12 weeks. At the end of the 12 weeks, a measure of liver function called alanine aminotransferase was significantly lower in the quercetin group. Overall, there was no significant differences in measures of VAT. However, in the subjects with a low high-density lipoprotein (HDL)-cholesterol, measures of VAT were lower in those taking quercetin (8).

7) Quercetin and Atherosclerosis

Given the potential for quercetin to have favorable effects on blood cholesterol, blood pressure, endothelial function, and VAT, interest in the potential for quercetin to have a role in the prevention of atherosclerosis overall has been discussed. The protective impact of quercetin on endothelial cells and its powerful antioxidant effects on reactive oxygen species suggest that it may favor healthier arteries resistance to plaque development. The role of quercetin in lowering chronic inflammation, foam cell production via oxidized LDL-cholesterol reductions, and even inducing autophagy have been postulated. For patients desiring to optimize their cardiovascular health, increasing quercetin on a daily basis has been identified as a promising approach (9).  

Conclusions

            Quercetin has many favorable activities that may benefit aspects of optimal cardiovascular health including blood pressure, lipids, endothelial function, and nitric oxide production. It is fortunate that it is found in many plant foods and it would be wise to increase these choices in a daily diet. Studies using supplemental quercetin as capsules or powders suggest promise for their use as a cardioprotective strategy and potentially having an impact on atherosclerosis development.

References

1. https://www.ars.usda.gov/ARSUserFiles/80400525/Data/Flav/Flav_R03.pdf
2. Bondonno, NP, Bondonno CP, Ward N, Woodman RJ, Hodgson JM, Croft KD. Enzymatically modified isoquercetin improves endothelial function in volunteers at risk of cardiovascular disease. Bt J Nutr. 2020 Jan;123(2):182-9.
3. Brull V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Muller C, Langguth P, Alteheld B, Fimmers R, Naaf S, Zimmerman BF, Stehle P, Egert S. Effects of quercetin-rich onion skin extract on 24 h ambulatory blood rpessure and endothelial functio in overweight-to-obese patients with (pre-) hypertension: a randomised double-blinded placebo-controlled cross-over trial. Br J Nutr. 2015 Oct;114(8):1263-77.
4. Kondratiuk VE, Synytsia YP. Effect of quercetin on the echocardiographic parameters of left ventricular diastolic function in patients with gout and essential hypertension. Wiad Lek 2018;71(8):1554-9.
5. Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD. Pure dietary flavonoids quercetin and epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 2008 Oct;88(4):1018-25.
6. Talirevic E, Jelena S. Quercetin in the treatment of dyslipidemia. Med Arh 2012;66(2):87-8.
7. Ven den Eynde MDG, Geleijnse JM, Scheijen JLM, Hanssen NMJ, Dower JI, Afman LA, Stehouwer CDA, Hollman PCH, Schalkwijk CG. Quercetin, but not epicatechin, decreases plasma concentrations of methylglyoxal in adults in a randomized, double-blind, placebo-controlled, crossover trial with pure flavonoids. J Nutr 2018 Dec;148(12):1911-6.
8. Nishimura M, Muro T, Kobori M, Nishira J. Effect of daily ingestion of quercetin-rich onion powder for 12 weeks on visceral fat: a randomised, double-blind, placebo-controlled, parallel-group study. Nutrients 2019 Dec;12(1):91.
9. Deng Q, Li XX, Fang Y, Chen X, Xue J. Therapeutic potential of qurecetin as an antiatherosclerotic agent in the atherosclerotic cardiovascular disease: a review. Evid Based Complement Alternat Med 2020 Jun;2020:5926381.