Flavonoids have been zesting up the health category since a Hungarian scientist, Dr. Albert Szent-Györgyi, discovered their phytochemical activity in 1938.1 Flavonoids were first extracted from oranges and were thought to be a new type of vitamin, often referred to as vitamin P. However, further research indicated that flavonoids were not a vitamin, rather, they are responsible for various protective measures of a plant and its coloring. Currently, there are about 6,000 known flavonoids. They play essential biological roles in plants, such as fruits, vegetables, flowers, wine, coffee, tea, etc., attracting pollinators and offering environmental stressor protection from the sun, drought, frost and more.2
There are six subclasses of flavonoids, which are abundant in most plant foods.3,4
1. Flavanols are known for their antioxidant properties and are found in broccoli, spinach, peppers, onions, apples, berries and tea.
2. Flavones are the pigments in blue and white flowering plants and work as a natural pesticide to protect leaves. They are also a potent nutrient supporting a healthy inflammatory response and are found in citrus, parsley, thyme, celery, peppermint and hot peppers.
3. Flavanones are known for their potent abilities to support a healthy inflammatory response and have been clinically shown to aid heart health,5 hyperglycemia,6-8 gut health,8,9 and may support healthy weight management.10 Flavanones are found in various citrus fruits, including lemons, oranges, limes, grapefruits and tangerines.
4. Falvan-3-ols are nutrient-dense in tea, cocoa-based items, grapes, berries, apples and red wine.
5. Isoflavones are also known for their beneficial role in a healthy inflammatory response and help to balance hormones. These are found in soy products and some legumes.
6. Anthocyanins are the natural pigment found in flowers and have been shown to support heart health.11 These are primarily found in berries, grapes and red wine.
Today, researchers have further investigated the role of flavonoid compounds and their therapeutic potential to benefit animal and human health.
Peeling Back the Research
Healthy Inflammatory Support
Research into flavonoids continues to show their potent ability to help support a proper inflammation response—specifically with the lemon flavonoids hesperidin and eriocitrin.12
One study on this flavanone blend found promising results against chronic inflammation over 12 weeks of supplementation. The study volunteers had undiagnosed hyperglycemia, which is recognized by the presence of low-grade systemic inflammation because of higher-than-normal blood glucose levels. The citrus flavonoids were able to provide significant support in the reduction of pro-inflammatory cytokines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP).6
Other studies have also observed the effect that even short-term intervention with citrus flavonoids can have on chronic inflammation. Eriocitrin and hesperidin helped to decrease the production of pro-inflammatory cytokines by reducing nitric oxide production and inhibiting the protein complex in charge of cytokine secretion, NFkB.13 This is done as the flavonoids help activate PPARg expression, inhibiting the expression of inflammatory cytokines and directing immune cells toward anti-inflammatory production.14,16
Super Antioxidant Support
Oxidative stress occurs when there’s an imbalance between free radical activity and antioxidant activity, which can damage cells and organs. Flavonoids have long been recognized as powerful antioxidants due to their ability to control the accumulation of reactive oxygen species (ROS) via scavenger ROS when they are formed.16 One recently published human clinical study investigated a branded flavonoid blend, Eriomin, comprised primarily of eriocitrin, on its antioxidant support on study volunteers with hyperglycemia. The double-blind, placebo-controlled study revealed that Eriomin improved the supplemented groups’ antioxidant capacity by six percent over 12 weeks compared to the placebo.6
Supporting Healthy Levels of Blood Glucose
Proper blood glucose management is a vital aspect of living healthfully. Unfortunately, the average American diet and the commonality of sedentary lifestyles make raised blood glucose levels all too prevalent. The Centers for Disease Control and Prevention (CDC) estimates that approximately 98 million American adults—more than one in three—have prediabetes.17 Several natural ingredients are known to support healthy glucose levels, including berberine, cinnamon, American ginseng, probiotics, magnesium18 and flavonoids.19
Citrus flavonoids, especially those found in lemons like eriocitrin and hesperidin, have been extensively researched for their effectiveness in supporting healthy blood glucose levels. One randomized, placebo-controlled human clinical study evaluated 103 volunteers with hyperglycemia and found that after 12 weeks of supplementation, participants had a statistically significant improvement in regulating healthy blood glucose levels, with 24 percent of the evaluated patients showing markers of increased glucose tolerance and returned to normal fasting blood sugar levels.6
A second double-blind, randomized, placebo-controlled crossover study evaluated the effects of a citrus flavonoid blend, branded Eriomin, on hyperglycemia. The study demonstrated its ability to significantly support healthy blood glucose levels (-5 percent) while increasing glucagon-like peptide 1 (GLP-1) by 17 percent and supporting a healthy inflammation response.7
Furthermore, a 2019 published review examined 240 articles on the blood glucose benefits of flavonoids, which illustrated a positive role in supporting blood sugar management.20
Boost Levels of GLP-1 Naturally
Glucagon-like peptide 1 (GLP-1), also known as incretin, is a hormone produced in the gut and released in response to food. It is reported to impact appetite and the release of insulin.20 GLP-1’s ability to bind to GLP-1 receptors triggers insulin production and removes glucose from the bloodstream, making it one of the most important hormones in helping manage healthy blood glucose levels. A multitude of scientific discoveries has shown that a proprietary blend of citrus flavonoids (Eriomin) can boost GLP-1 levels naturally by up to 22 percent and reduce hyperglycemia after only 12 weeks of intervention.6-8 Besides its blood sugar control benefits, recent research has shown that GLP-1 can also support healthy weight management.21
Cardiovascular Support
In the United States, heart disease is the leading cause of death, and high blood pressure, high blood cholesterol, obesity and smoking are key risk factors.22 Several health authorities are coming together to better educate the public about the critical importance of taking care of our hearts and reducing risk. Some of these include eating a healthy diet, maintaining a healthy weight, increasing physical activity, avoiding alcohol, quitting tobacco, and regularly checking blood pressure and blood sugar levels.23
Diets rich in flavonoids continue to gain attention for their heart health benefits. Specifically, they have been shown to have positive benefits on blood pressure24 and several cardiovascular parameters. One double-blind, placebo-controlled published clinical review investigated a patented blend of natural citrus and palm fruit extracts, branded Sytrinol, on its heart health potential. The researchers found that in four weeks at 270 mg/day, Sytrinol significantly modulated various markers of cardiovascular health, including cholesterol improvements (-27 percent), LDL cholesterol (-25 percent), LDL: HDL ratio (-28 percent), and triglyceride levels (-31 percent).5 Additionally, a meta-analysis of 14 prospective studies published between 1996 and 2012 reported that higher intakes in each flavonoid subclass were significantly associated with improved cardiovascular function.25 Another review published in 2020 also concluded that flavonoids are critical nutrients that play an important role in supporting heart health properties.26
Flavonoids showcase the remarkable synergy between nutrition and well-being and, through clinical research, continue to show significant promise for their healthy inflammatory response support, potent antioxidant activity, blood sugar support, and much more. So, when it comes time to “add some color to your diet,” embracing these plant-based powerhouses will help nurture our bodies for the long run. NIE
References:
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2 Panche AN, Diwan AD, Chandra SR. Flavonoids: An overview. Journal of Nutritional Science. 2016;5(e47). doi:https://doi.org/10.1017/jns.2016.41.
3 Watson K, Hatanaka, RDN, L.D. M, Matysiak S. Everything You Need to Know About Flavonoids. Healthline. Published October 23, 2019. www.healthline.com/health/what-are-flavonoids-everything-you-need-to-know#sources.
4 The thinking on flavonoids. Harvard Health. Published October 1, 2020. www.health.harvard.edu/mind-and-mood/the-thinking-on-flavonoids.
5 Roza JM, Xian-Liu Z, Guthrie N. Effect of citrus flavonoids and tocotrienols on serum cholesterol levels in hypercholesterolemic subjects. Alternative Therapies in Health and Medicine. 2007;13(6):44-48. https://pubmed.ncbi.nlm.nih.gov/17985810/.
6 Ribeiro CB, Ramos FM, Manthey JA, Cesar TB. Effectiveness of Eriomin in managing hyperglycemia and reversal of prediabetes condition: A double-blind, randomized, controlled study. Phytotherapy Research. 2019;33(7):1921-1933. doi:https://doi.org/10.1002/ptr.6386.
7 Thais Borges Cesar, Maria F, Carolina Barbosa Ribeiro. Nutraceutical Eriocitrin (Eriomin) Reduces Hyperglycemia by Increasing Glucagon-Like Peptide 1 and Downregulates Systemic Inflammation: A Crossover-Randomized Clinical Trial. Journal of Medicinal Food. 2022;25(11):1050-1058. doi:https://doi.org/10.1089/jmf.2021.0181.
8 Maria F, Carolina Barbosa Ribeiro, Thaís Borges César, et al. Lemon Flavonoids Nutraceutical (Eriomin) Attenuates Prediabetes Intestinal dysbiosis: a Double-blind Randomized Controlled Trial. Food Science and Nutrition. 2023;11(11). doi:https://doi.org/10.1002/fsn3.3654.
9 Cesar T, Salgaço MK, Mesa V, Sartoratto A, Sivieri K. Exploring the Association between Citrus Nutraceutical Eriocitrin and Metformin for Improving Pre-Diabetes in a Dynamic Microbiome Model. Pharmaceuticals. 2023;16(5):650. doi:https://doi.org/10.3390/ph16050650.
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12 Pérez-Cano, F. J., & Castell, M. (2016). Flavonoids, Inflammation and Immune System. Nutrients, 8(10), 659. https://doi.org/10.3390/nu8100659.
13 Lee, J.K. (2011). Anti-inflammatory effects of eriodictyol in lipopoly- saccharide-stimulated raw 264.7 murine macrophages. Arch Pharm Res, 34 (4), 671-9. doi: 10.1007/s12272-011-0418-3.
14 Gamo, K., Miyachi, H., Nakamura, K., Matsuura, N. (2014). Hesperetin glucuronides induce adipocyte differentiation via activation and ex- pression of peroxisome proliferator-activated receptor-γ. Biosci Bio- technol Biochem, 78(6), 1052-9. doi: 10.1080/09168451.2014.910097.
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16 Dias MC, Pinto DCGA, Silva AMS. Plant Flavonoids: Chemical Characteristics and Biological Activity. Molecules. 2021;26(17):5377. doi:https://doi.org/10.3390/molecules26175377.
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22 CDC. Heart Disease Facts. Centers for Disease Control and Prevention. Published May 15, 2023. www.cdc.gov/heartdisease/facts.htm.
23 World Health Organization. How to Take Care of Your Heart Health. www.who.int. Published February 14, 2020. www.who.int/philippines/news/feature-stories/detail/how-to-take-care-of-your-heart-health.
24 Jennings A, Koch M, Bang C, Franke A, Lieb W, Cassidy A. Microbial Diversity and Abundance of Mediate the Associations between Higher Intake of Flavonoid-Rich Foods and Lower Blood Pressure. Hypertension. 2021;78(4):1016-1026. doi:https://doi.org/10.1161/hypertensionaha.121.17441.
25 Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid Intake and Risk of CVD: a Systematic Review and meta-analysis of Prospective Cohort Studies. British Journal of Nutrition. 2013;111(1):1-11. doi:https://doi.org/10.1017/s000711451300278x.
26 Ciumărnean L, Milaciu MV, Runcan O, et al. The Effects of Flavonoids in Cardiovascular Diseases. Molecules. 2020;25(18):4320. doi:https://doi.org/10.3390/molecules25184320.
Rob Brewster is the president of California-based Ingredients by Nature. As a third-generation ingredient manufacturer for the natural products industry, Brewster is proud to be part of the health and wellness world. He followed in his grandfather’s and father’s footsteps, helping their company Brewster Foods grow since he joined in the 1990s and then partnering with Syntech to form Ingredients by Nature, a world leader in citrus bioflavonoids and extracts. As president, Brewster invests heavily in citrus flavonoid science for condition-specific applications and holistic wellness. For more information, visit IngredientsbyNature.com.
