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Anthocyanins as an Adjunct in Heart Health

Douglas Jacoby, MD, FACC, FNLA, FASPC, Board Certified Cardiologist and Lipidologist
Kim Biedermann, PhD Chief Science Officer at Mend
Alexa Abdelaziz, PhD, Director of Research and Development at Mend

This article is intended for a professional audience. Consumers should always consult with their physician before considering any natural products for their health.

Preface

Many in the medical and scientific communities view claims from natural products with a level of skepticism. This is founded, as there is often a dearth of data and/or the claims don’t stand on a particularly strong foundation of science. This seems to be shifting, however and more companies in the natural products world are investing in science and strong data. One compound that has caught our attention are anthocyanins, in particular ones extracted from bilberries and black currants, which now have more than 20 published randomized trials. While the outcomes data still need to be established, the compound does impact several biomarkers of heart health concern in a positive direction and with a compelling delta. In this paper, we review the published science on anthocyanins as a potential adjunctive therapy in heart health. To be clear, there are no natural products that replace the benefits of a healthy lifestyle, including eating healthy and exercising. There are also no natural products that should be used instead of well proven risk reducing medications, such as statins. However, we know that there is strong consumer appetite for natural solutions, and many patients will take supplements whether or not providers recommend them; thus, as professionals we favor guiding patients with an interest in supplements to compounds that have the strongest science supporting them.

Context

Heart disease continues to be the leading cause of death among both men and women in people of most racial and ethnic groups in the United States. The statistics continue to be alarming, according to the CDC, one person dies every 36 seconds, 659 thousand per year from heart disease – nearly 25% of all deaths in the country. In the US, we are spending roughly $400 billion per year in services, medicines and lost productivity due to cardiovascular disease.

What are anthocyanins?

Anthocyanins are the largest group of water-soluble pigments in the flavonoid class. They are powerful antioxidants involved in scavenging radicals and chelating metal ions and are responsible for the red, blue, and purple colors of many fruits and vegetables. In particular, bilberries and blackcurrants naturally contain the highest levels of anthocyanins vs. other foods. In nature, six main anthocyanins are found and classified according to the number and location of the hydroxyl and methoxyl group attached to the flavan nucleus. The six main anthocyanins are pelargonidin, cyanidin, delphinidin, malvidin, peonidin, and petunidin, with cyanidin as the most widely occurring ^1,2.

Safety

Addressing safety at the outset, as that is the primary concern for any intervention, this compound is classified by the FDA as “GRAS”, or Generally Recognized As Safe. The FDA places natural compounds in this category when there is sufficient data on its safety profile to be allowed for widespread consumption. Furthermore, the compound has been utilized in natural supplements in Europe and Asia for more than two decades, with no known reported adverse events or contraindications.

Scientific support of heart health with anthocyanins

A number of epidemiological studies have shown positive correlations between flavonoids and decreased risk of cardiovascular disease (CVD)⁵ and anthocyanin scientific studies have been trending in recent years as interest in these compounds for their health benefits grows. Numerous independent human clinical trials performed with a specific combination of anthocyanins from bilberries and blackcurrants have shown to affect key risk factors that drive the progress of CVD. CVD is a multi-component pathology with many risk factors that accelerate disease. These key risk factors include inflammation, atherosclerosis, oxidative stress, hypertension, endothelial function, and high cholesterol, among others.

Inflammation and Atherosclerosis

Anthocyanins from a standardized extract of blackcurrants and bilberries are able to interfere in the inflammatory cascade. This is done by inhibiting NF-κB and C-reactive protein (CRP) and therefore decreasing the plasma concentrations of proinflammatory cytokines and other inflammatory mediators. Proinflammatory cytokines, especially CRP, are also involved in the pathogenesis of atherosclerosis. In one parallel- designed placebo- controlled trial, after 3 weeks of anthocyanin supplementation, significant decreases were found in proinflammatory mediators such as Interleukin 8 (IL-8), IL-4, IL-13, and Interferon-α (IFN-α) levels⁶. Another double-blind trial showed after anthocyanin supplementation, decreased levels of serum CRP, soluble vascular cell adhesion molecule-1 (VCAM-1) and plasma interleukin 1β (IL-1β)⁷. Two studies demonstrated that bilberry and blackcurrant anthocyanins suppressed platelet activity and thus the risk of thrombogenesis, platelet hyperactivation and hyper-aggregation in overweight/obese and sedentary populations^13-14. Reducing these key inflammatory may prevent the pathogenesis of disease.

Lipid Profile and Endothelial Function

Studies show that anthocyanins from bilberry and blackcurrants are able to decrease LDL- cholesterol levels and increase HDL- cholesterol levels in people with risk factors for CVD development⁸. Overall, from 5 RCTs conducted, an average reduction in LDL cholesterol of 10% and an average increase in HDL cholesterol of 14% was observed¹¹. Anthocyanin supplementation also has been shown to lead to increases in flow mediated dilation (FMD) suggesting better blood flow and improved endothelial function⁹.

Oxidative Stress

Anthocyanins are powerful antioxidants. In one study, anthocyanin supplementation caused an increase in Total Radical-trapping Antioxidant Parameter (TRAP) and Ferric ion Reducing Antioxidant Power (FRAP)¹⁰. These are critical parameters to assess the free radical scavenging capabilities of a product and determine its antioxidant capacity. Elevated oxidative stress and inflammation are key risk factors cross-promoting one another and potentially resulting in the progression of heart disease. Anthocyanin supplementation has been shown to improve oxidative stress markers such as total superoxide dismutase (T-SOD),urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-iso-PGF2α), and malonaldehyde (MDA)¹². This suggests that improvements in oxidative stress, yet another potential benefit in improving cardiovascular health.

Anthocyanin Sources

Natural sources with high anthocyanin content are berries, red grapes, cherries, red cabbage, eggplant, red wines, and the black variants of rice and soybean. Interestingly, there is a difference in the type and concentration of anthocyanins available depending on the berry (See Figure 1)

As shown in Figure 1, the relative anthocyanin content of common berries can range from low content like black grapes to high content like bilberries. Bilberries and blackcurrants are a balanced anthocyanin source, containing anthocyanins with different hydroxylation patterns and a variety of sugar side chains. Together, these two fruits exhibit synergistic effects of the main antioxidant anthocyanin components. This combination of fruits and their extraction processes helps balance out the fruit’s seasonal fluctuations, ensuring stable compositions and consistent dosages.

Our Intake

Most people in countries around the world have an intake of anthocyanins well below the recommended average of 80mg / day⁴ (Figure 2).

Conclusion

Overall, anthocyanins possess many potential health benefits and the strongest may be for cardiovascular health. Most people are not getting adequate levels of anthocyanins from their diet. Anthocyanins sourced from blackcurrants and bilberries provide a rich, synergistic profile which may improve cardiovascular health by improving endothelial dysfunction, lowering LDL cholesterol, reducing inflammation, and decreasing platelet activation and oxidative stress.

Data from over 20 years of clinical trials investigating specifically the combination of anthocyanins in blackcurrants and bilberries consistently show reduction in these key risk factors involved in the progression of CVD which shows great promise for cardiovascular benefit. For patients who plan to take supplements to reduce their cardiovascular risk, this would be a good choice because it has more evidence than most other available supplements and it consistently moves biomarkers in the right direction. Future research will help us continue to understand and elucidate these impacts.

References

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2] Bei R.; Masuelli L.; Turriziani M.; Volti G.; Malaguarnera M.; Galvano F., Impaired expression and function of signaling pathway enzymes by anthocyanins: role on cancer prevention and progression, Current Enzyme Inhibition, 2009, 5, 4, 184-197.

3] AFI Webinar 1 – Anthocyanins. October 2020

4] Igwe EO, Charlton KE, Probst YC. Usual dietary anthocyanin intake, sources and their association with blood pressure in a representative sample of Australian adults. J Hum Nutr Diet. 2019 Oct;32(5):578-590. doi: 10.1111/jhn.12647. Epub 2019 Mar 27. PMID: 30916431.

5] Wallace T., Anthocyanins in cardiovascular disease, Advances in Nutrition, 2011, 2, 1-7.

6] Karlsen A.; Retterstøl L.; Laake P.; Paur I.; Kjølsrud-Bøhn S.; Sandvik L.; Blomhoff R., Anthocyanins inhibit Nuclear Factor-KB activation in monocytes and reduce plasma concentrations of pro-inflammatory mediators in healthy adults, The Journal of Nutrition, 2007, 137, 1951-1954

7] Zhu Y.; Ling W.; Guo H.; Song F.; Ye Q.; Zou T.; Li D.; Zhang Y.; Li G.; Xiao Y.; Liu F.; Li Z.; Shi Z.; Yang Y., Anti-inflammatory effect of purified dietary anthocyanin in adults with hypercholesterolemia: a randomized controlled trial, Nutrition, Metabolism & Cardiovascular Diseases, 2013, 23, 843-849.

8] Qin Y.; Xia M.; Ma J.; Hao Y.; Liu J.; Mou H.; Cao L.; Ling M., Anthocyanin supplementation improves serum LDL- and HDL-cholesterol concentrations associated with the inhibition of cholesteryl ester transfer protein in dyslipidemic subjects, The American Journal of Clinical Nutrition, 2009, 90, 485-492.

9] Zhu Y.; Xia M.; Yang Y.; Liu F.; Li Z.; Hao Y.; Mi M.; Jin T.; Ling W., Purified anthocyanin supplementation improves endothelial function via NO-cGMP activation in hypercholesterolemic individuals, Clinical Chemistry, 2011, 57, 11, 1524-1533.

10] Li D.; Zhang Y.; Liu Y.; Sun R.; Xia M., Purified anthocyanin supplementation reduced dyslipidemia, enhances antioxidant capacity, and prevents insulin resistance in diabetic patients, The Journal of Nutrition, 2015.

11] Zhu Y.; Huang X.; Zhang Y.; Wang Y.; Liu Y.; Sun R.; Xia M., Anthocyanin supplementation improves HDL-associated paraoxonase 1 activity and enhances cholesterol efflux capacity in subjects with hypercholesterolemia, The Journal of Clinical Endocrinology & Metabolism, 2014, 99, 2, 561-569.

12] Zhang, H., Xu, Z., Zhao, H., Wang, X., Pang, J., Li, Q., Yang, Y., & Ling, W. (2020). Anthocyanin supplementation improves anti-oxidative and anti-inflammatory capacity in a dose-response manner in subjects with dyslipidemia. Redox biology, 32, 101474. https://doi.org/10.1016/j.redox.2020.101474.

13] Thompson et al Br J Nutr (2017) 118:368–374

14] Thompson et al Journal of Functional Foods 32 (2017) 131–138

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