1. Flavonols and Their Impact on Coronary Heart
Disease and Atherosclerosis
Claire Calhoun, Ashtin Spies, McKenzie Galvin
Department Of Food Science & Human Nutrition, Colorado State University, Fort Collins, CO
Fall 2015
ABSTRACT
Phytochemicals are bioactive compounds that fall under the category of phenolic
compounds, which are further broken down into flavonoids and flavonols.4 Research has
shown that an increased flavonol intake helps reduce plaque buildup that can result in
atherosclerosis and Coronary Heart Disease by impacting various mechanisms
including LDL oxidation, adhesion molecule expression and anti-inflammatory
responses.Two flavonols highlighted in research literature, quercetin and kaempferol,
exhibit this protective action and are found in a wide variety of foods.
The majority of research has focused on the function of pure flavonols forms and may not
be indicative of the behaviors and qualities of metabolized, bioavailable flavonol
forms. More research on the in vivo cardiovascular protective qualities of flavonols
needs to be implemented.
OBJECTIVES
•Coronary Heart Disease: how flavonols act as antioxidants
•Flavonols role in preventing atherosclerosis
•Quercetin and Kaempferol, and their beneficial qualities
•Bioavailable flavonol metabolites compared to pure form flavonols
•Simple ways to increase flavonol intake
PHYSIOLOGICAL ASPECTS
The buildup of plaque within blood vessels, or atherosclerosis, is indicative of CHD. This
process begins when LDL accumulates and begins to oxidize in the sub-endothelial
space which promotes vascular cells to produce adhesion molecules like MCP-1(a
chemoattractant),VCAM-1, and ICAM-1.7 Adhesion molecules allow monocytes entry
into the endothelial space where they turn into macrophages. Once fully oxidized, LDL
is recognized by scavenger receptors on newly formed macrophages that phagocytize
LDL and form foam cells. The accrual of foam cells in the sub-endothelial space leads to
atherosclerosis.8
Flavonols work to prevent this accumulation through inhibiting LDL-oxidation, platelet
aggregation, and suppressing adhesion molecules expression. Therefore, flavonols can
help decrease the prevalence of CHD and atherosclerosis by decreasing the associated
chronic inflammatory response.9,10 Zutphen Elderly study reported a 50% reduction in
CHD mortality with flavonoid intakes of ~30 mg/day vs. <19 mg/day. Quercetin and
kaempferol were the two main flavonols used.11 For reference, 2/3 cups of raw red onion
alone contribute roughly 50 mg of quercetin.1
IMPLICATIONS
Much of the research available on flavonols’ role in CHD prevention and other
cardiovascular diseases is based on in vitro studies using pure forms of flavonols.3 When
obtained through a dietary source, however, flavonols are broken down during digestion
into a collection of bioavailable forms, or metabolites.7 Also, dietary flavonols found in
plants are a source of protection for the plant, and are often found in glycosylated versus
pure forms.6
The differences between bioavailable forms and pure flavonols account for some of the
differences in in vitro and in vivo studies.6 For example, a combination of multiple
flavonols or flavonol metabolites may have a collective impact, as supported by the fact
that whole foods are often more impactful than supplements.14 Also, flavonols have been
shown to have a different impact than other antioxidants, so their metabolite structures
may be important in their role of other mechanism-based preventative properties.6,7 With
this in mind, it is important for future research to study the impact of bioavailable flavonol
metabolites when implicating their direct impact on CHD prevention.
CONCLUSION
Coronary Heart Disease is an increasing problem in the United States but recent research
suggests that sufficient flavonol intake provides a protective effect against this disease.4,5,8
Flavonols exhibit anti-inflammatory properties and are shown to reduce LDL oxidation
and adhesion molecule expression, decreasing the prevalence of
atherosclerosis. Flavonol-rich plant foods, like kale and onions, provide roughly 50 mg of
flavonols in a 100 gram serving.12 Incorporating sufficient amounts of a variety of fruits,
vegetables, wine and tea into your diet is a simple way to take advantage of flavonols’
beneficial properties related to cardiovascular health.
REFERENCES
1. Coronary Heart Disease. American Heart Association Web site. www.heart.org. Published 2015. Accessed October 20, 2015.
2. Harris, M. Cardiovascular Disease and Hypertension . Lecture. 2015.
3. Brieger K, Schiavone S, Miller FJ Jr, Krause KH. Reactive oxygen species: from health to disease. Swiss Med Wkly. 2012; 142:
13659. doi: 10.4414/smw.2012.13659
4. Kris-Etherton P, Hecker K, Bonanome A et al. Bioactive compounds in foods: their role in the prevention of cardiovascular disease and
cancer. The American Journal of Medicine. 2002;113(9):71-88. doi:10.1016/s0002-9343(01)00995-0.
5. Howard B, Kritchevsky, D. Phytochemicals and Cardiovascular Disease: A Statement for Healthcare Professionals from the American
Heart Association. Circulation. 2007; 95: 2591-2593. doi: 10.1161/01.CIR.11.2591
6. Alexandra B. Bentz. A Review of Quercetin: Chemistry, Antioxoidant Properties, and Bioavailability. Journal of Young Investigators.
2009. http://www.jyi.org/issue/a-review-of-quercetin-chemistry-antioxidant-properties-and-bioavailability/
7. Tribolo, S et al. Comparitive effects of quercetin and its predominant human metabolites on adhesion molecule expression in
activated human vascular endothelial cells. Aterosclerosis. 2008; 197 50-56. doi: 10.1016/j.atheroslcerosis.2007.040
8. Epstein F, Diaz M, Frei B, Vita J, Keaney J. Antioxidants and Atherosclerotic Heart Disease. New England Journal of Medicine.
1997;337(6):408-416. doi:10.1056/nejm199708073370607.
9. Libby P, Ridker P, Maseri A. Inflammation and Athersclerosis. Circulation. 2002; 105: 1135-1143. doi: 10.1161/hc0902.104353
10. Pan M, Lai C, Ho C. Anti-inflammatory activity of natural dietary flavonoids. Food & Function. 2010;1(1):15. doi:10.1039/c0fo00103a.
11. Hertog M, Feskens E, Kromhout D et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study.
The Lancet. 1993;342(8878):1007-1011. doi:10.1016/0140-6736(93)92876-u.
12. United States Department of Agriculture. Flavonoid Content of
Vegetables. http://www.ars.usda.gov/SP2UserFiles/Place/80400525/Articles/AICR03_VegFlav.pdf. Accessed November 1, 2015.
13. Mari Hämäläinen, Riina Nieminen, Pia Vuorela, Marina Heinonen, and Eeva Moilanen, “Anti-Inflammatory Effects of Flavonoids:
Genistein, Kaempferol, Quercetin, and Daidzein Inhibit STAT-1 and NF- B Activations, Whereas Flavone, Isorhamnetin, Naringenin, and
Pelargonidin Inhibit only NF- B Activation along with Their Inhibitory Effect on iNOS Expression and NO Production in Activated
Macrophages ,” Mediators of Inflammation, vol. 2007, Article ID 45673, 10 pages, 2007. doi:10.1155/2007/45673
14. Rui Hai Liu. Potential Synergy of Phytochemicals in Cancer Prevention: Mechanism of Action. J Nutr. 2004; 134 (12): 34795-34855.
15. Arts Ilja CW, Hollman Peter CH. Polyphenols and disease risk in epidemiologic studies. Am J Clin Nutr. 2005; 81 (1): 3175-3255.
16. Vita Joseph A. Polyphenols and cardiovascular disease: effects on endothelial and platelet function. Am J Clin Nutr. 2005; 81 (1):
2925-2975.
17. Aviram M, Dornfeld L, Kaplan M, et al. Pomegranate juice flavonoids inhibit low-density lipoprotein oxidation and cardiovascular
diseases: studies in atherosclerotic mice and in humans. Drugs Under Experimental and Clinical Research. 2002; 28(2): 49-62.
18. Hirano R, Sasamoto W, Matsumoto A, et al. Antioxidant Ability of Various Flavonoids against DPPH Radicals and LDL Oxidation.
Journal of Nutritional Science and Vitaminology. 2001; 47 (5): 357-362.
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site. http://www.sabiosciences.com/pathway.php?sn=LDL_Oxidation_in_Atherogenesis. Published 2012. Accessed October 15,
2015.
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http://europepmc.org/abstract/med/25828593. Accessed October 20, 2015.
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Anti-inflammatory activity of natural dietary flavonoids. Reprinted from Food & Function.10
INTRODUCTION
Coronary Heart Disease (CHD) is the leading cause of death in the United States, and
results in over 375,000 deaths per year.1
Risk Factors for CHD:
• Age (males >45, females >55) • High LDL-c
• Smoking • Low HDL-c
• Hypertension • Insulin Resistance
• Diabetes • Abdominal obesity
• Previous History of CHD • High Triglycerides
CHD’s alarming impact has caused increasing amounts of research to target the
prevention of this disease. Human cells are unstable by nature. Radical oxygen
species (ROS) can easily act on our cells, damaging them and, in turn, contribute to
various health conditions such as CHD.3 Due to their known antioxidant properties,
phytochemicals have the ability to prevent ROS damage. Flavonols are found in a
variety of fruits, vegetables, nuts, legumes, soy, tea, and wine. Tea is the main dietary
source of flavonols.5,6
RELATED NUTRIENTS
Kaempferol and Quercetin are two of the main known and studied flavonols.These can be
found in a variety of plant based foods.4
Quercetin Kaempferol
Found in:
• onions
• broccoli
• apples
• grapes
• wine
• tea
• leafy green vegetables4
It decreases the expression of the adhesion
molecules VCAM-1, ICAM-1, and MCP-1.6
Without these molecules, LDL is not able to
attach to the endothelial layer of the vessel
during the early stages of
atherosclerosis. 64mg/kg of body weight of
quercetin showed significant inhibition of
atherosclerotic lesion.10
Found in:
• endives
• leeks
• broccoli
• radish
• black tea
• grapefruit
Studies on flavonoids’ anti-inflammatory
effects identify kaempferol, along with a few
other flavonols, to inhibit inducible nitric
oxide synthase (iNOS) transcription factors
as a way of STAT-1 and NF- β inhibition.This
inhibition is shown to explain some of
flavonoids and flavonols’ anti-inflammatory
properties.13
Recreated from various sources