Ingredients for heart and cardiovascular health

According to the World Health Organization (WHO), cardiovascular diseases (CVD) are a group of disorders that affect the function of the heart and blood vessels, including coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, congenital heart disease, deep vein thrombosis, and pulmonary embolism. CVD is the leading cause of death worldwide, with an estimated 17.9 million deaths each year1. According to the WHO, the key factors for CVD are listed in Table 1.

Heart and cardiovascular diseases are the leading cause of mortality worldwide. Caused by factors such as an unhealthy diet, insufficient physical activity, smoking, and stress, they require increased attention and timely preventive measures. A combination of appropriate food and dietary supplements can help reduce risk factors.

Although heart diseases are the leading cause of death worldwide, they can largely be prevented. Dietary supplements have great potential for heart health in addition to adopting healthy lifestyle habits. In the following text, we will discuss several ingredients in dietary supplements that have actual evidence of their effectiveness.

Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have shown numerous benefits for the heart. Their positive effects include reducing triglyceride levels, blood pressure, and inflammatory processes in the body. Additionally, omega-3 fatty acids improve blood vessel elasticity and reduce the risk of heart attack and stroke2,3

Coenzyme Q10 is a substance naturally found in the body that plays an important role in energy production. Furthermore, research has shown that coenzyme Q10, in the form of a dietary supplement, can improve heart function, reduce the risk of heart disease, and support recovery after a heart attack. It acts as an antioxidant and helps maintain a healthy heart muscle4

Resveratrol is a natural compound found in red wine, black grapes, and some other plants. Studies have shown that it has antioxidant properties and can improve heart health. It works by reducing inflammation, protecting blood vessels from damage, and promoting circulation5

Black garlic extract is gaining attention as a potential dietary supplement for heart health. It is obtained through the fermentation of fresh white garlic under specific conditions. This process creates a unique combination of active compounds that can have a beneficial effect on the cardiovascular system. Research has shown that black garlic extract can provide the following benefits for the heart6,7,8:

• Antioxidant action: black garlic extract is rich in antioxidants that can help reduce oxidative stress in the body. Oxidative stress can damage blood vessels and contribute to the development of heart diseases.

Cardiovascular diseases (CVDs) are the leading cause of death globally.

An estimated 17.9 million people died from CVDs in 2019, representing 32% of all global deaths. Of these deaths, 85% were due to heart attack and stroke.

Over three quarters of CVD deaths take place in low- and middle-income countries.

Out of the 17 million premature deaths (under the age of 70) due to noncommunicable diseases in 2019, 38% were caused by CVDs.

Most cardiovascular diseases can be prevented by addressing behavioural risk factors such as tobacco use, unhealthy diet and obesity, physical inactivity and harmful use of alcohol.

It is important to detect cardiovascular disease as early as possible so that management with counselling and medicines can begin.

• Cholesterol reduction: some studies suggest that black garlic extract can lower total cholesterol and LDL cholesterol (bad cholesterol) levels in the blood. High cholesterol levels are known to increase the risk of heart disease.

• Blood pressure reduction: preliminary research indicates that black garlic extract may have a mild hypotensive effect, meaning it can lower blood pressure. This can be beneficial for individuals with high blood pressure.

• Anti-inflammatory action: black garlic extract contains compounds with anti-inflammatory properties. Inflammation is an important factor in the development of heart diseases, so the anti-inflammatory action of black garlic can be beneficial for heart health.

Despite these promising results, further research is needed to better understand the mechanisms of action and confirm the benefits of black garlic extract for the heart.

Hawthorn (Crataegus spp.) is a plant traditionally used to support heart and cardiovascular health.

Studies have shown that its extract can improve blood flow, regulate blood pressure, reduce inflammation, and support heart function9-12. The effects are attributed to the presence of flavonoids, procyanidins, and other compounds with antioxidant and anti-inflammatory properties.

Hawthorn is used to treat symptoms of mild to moderate heart failure, angina, and high blood pressure. It has also been found to be helpful in alleviating symptoms of arrhythmias and promoting a healthy heart rhythm. However, it is important to note that each individual may respond differently to hawthorn. Consultation with a doctor is recommended before taking hawthorn preparations or making changes to the treatment regimen. Special attention should be paid to patients who are prescribed digitalis, and they should be informed that hawthorn preparations may enhance the effect of the medication. Therefore, the recommendation is either to adjust the medication dosage (under medical supervision) or avoid simultaneous consumption.

In Croatia, two species of hawthorn are on the list of permitted substances for dietary supplements according to the current regulations: Crataeguslaevigata and Crataegus monogyna , with limitations: the permitted ingredients are leaf and flower, and the dosage is limited to a maximum equivalent of 1,5 g/day of the starting herbal material (leaf and flower). The dietary supplement label must include the text: "Should not be used for more than 4 months without interruption. Individuals taking medications should consult a doctor before use. Not recommended for pregnant and breastfeeding women."

In the Czech Republic, there is a limitation that dried leaves, flowers, and fruits can be used in a maximum quantity of 1,000 mg per day.

Hawthorn has several on-hold health claims for cardiovascular health and circulation.

Tomato Extract - several scientific articles discuss the beneficial effects of tomato extract on cardiovascular health. Different scientific studies suggest that lycopene, the main bioactive compound in tomatoes, may have various beneficial physiological effects on improving cardiovascular health through platelet aggregation and related vascular mechanisms13 .

The European Food Safety Authority (EFSA) has is- sued a scientific opinion (Figure 1) on the substantiation of a health claim for water-soluble tomato concentrate sold under the patented name Fruitflow® in two forms: water-soluble tomato concentrate syrup (WSTC I) or powder (WSTC II). The claimed effect is a "reduction in platelet aggregation," and the target population is healthy adults aged between 35 and 70 years. The panel considers that maintaining normal platelet aggregation is beneficial for human health14

In a double-blind, randomized, controlled trial (RCT), a significant reduction (compared to placebo) of 825% in platelet aggregation was observed 3 hours after consuming tomato extract, corresponding to 3 g and 9 g of WSTC I in 200 mL of orange juice15

Berberine - Insulin resistance can worsen cardiovascular health over time, as chronically elevated blood sugar can cause tissue damage and elevated blood pressure.

Berberine is a bioactive compound that can be extracted from a group of shrubs called Berberis, such as Berberisvulgaris L., and Berberis aristata DC. Technically, it belongs to a class of compounds called alkaloids. Berberine is an activator of AMP-activated protein kinase (AMPK), which means it can help attract glucose and lipids into cells, allowing them to be used as energy.

In addition to reducing blood sugar, which can be compared to diabetes medication (Metformin), berberine is a powerful agent for lowering blood glucose levels that can be beneficial for individuals with impaired glucose regulation. When combined with lifestyle interventions, berberine can greatly improve glucose levels (HbA1c) and help lower high cholesterol in individuals with type 2 diabetes17

Hydroxytyrosol is a polyphenolic compound found in olive oil that is well-known for its antioxidant, anti-inflammatory, and antiatherogenic effects. It can also be found in olive water, a by-product of olive oil production. It is one of the components contributing to the positive effects of the Mediterranean diet on health. It has been proven to have potential therapeutic and preventive properties in cardiovascular diseases (Figure 2). A review of scientific literature on hydroxytyrosol in in vitro and in vivo models, as well as in clinical studies on humans, describes its potential biological effects on cardiovascular health18

EFSA has assigned a health claim: "olive oil polyphenols contribute to the protection of blood lipids from oxidative stress." The claim can only be used for olive oil that contains at least 5 mg of hydroxytyrosol and its derivatives (e.g., oleuropein complex and tyrosol) per 20 g of olive oil. To use this claim, consumers must be provided with information that the beneficial effect is achieved through the daily consumption of 20 g of olive oil.

Red yeast rice extract - according to European regulation, red yeast rice extract is considered a preparation that can reduce cholesterol levels due to its content of monacolin K. Monacolin K is similar to the active ingredient in statins, pharmaceutical drugs used to lower cholesterol.

The use of red fermented rice extract has significantly changed with the adoption of Commission Regulation (EU) 2022/860 on June 1, 2022, amending Annex III of Regulation (EC) No 1925/2006 of the European Parliament and of the Council, regarding monacolins from red fermented rice.

Red fermented rice is obtained by fermenting rice using the Monascuspurpureus yeast, resulting in the production of monacolins, primarily monacolin K. In China, it has traditionally been used as a food colorant and as a traditional remedy to promote digestion and blood circulation. It is not approved for use as a food colorant in the EU, as it is not listed in Regulation (EC) No 1333/2008 of the European Parliament and of the Council on food additives.

Unlike the previous limit of 10 mg of monacolin K from red fermented rice in a single portion for daily consumption, the product must now contain less than 3 mg of monacolin in a single, daily portion. The packaging must also indicate the number of individual servings of the product for the maximum allowed daily consumption and provide a warning not to consume a daily dose of 3 mg or more.

The packaging must state the monacolin content per serving of the product and include the following warnings: "The product should not be consumed by pregnant women, breastfeeding women, children under 18 years of age, and adults over 70 years of age";

"If you have any health problems, consult a doctor before consuming this product"; "The product should not be consumed if you are taking cholesterol-lowering medications"; "The product should not be consumed if you are already taking other products that contain red fermented rice."

Conclusion

Dietary supplements can be beneficial as part of a comprehensive approach to maintaining cardiovas- cular health. Omega-3 fatty acids, coenzyme Q10, black garlic, hawthorn, resveratrol, and berberine are some of the ingredients in dietary supplements that have shown beneficial effects on heart health and have an appropriate safety profile.

The ingredients of finished products and combinations of active substances have greatly changed after the adoption of Commission Regulation (EU) 2022/860 on June 1, 2022, amending Annex III. Prior to this regulation, a large number of dietary supplements aimed at cardiovascular health were based solely on red yeast rice extract and monacolin K. Therefore, this topic gains further significance as new ingredients that can replace products containing 10 mg of monacolin K, but with a better safety profile, become popular.

The application of the results of past and future research will demonstrate the best direction for developing new products to achieve optimal support for cardiovascular health.

References:

1 https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-%28cvds%29

2 Mozaffarian D, Wu JH. (2011). Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 58(20):2047-67.

3 Yan J, Liu M, Yang D, Zhang Y, An F. Efficacy and Safety of Omega-3 Fatty Acids in the Prevention of Cardiovascular Disease: A Systematic Review and Meta-analysis [published online ahead of print, 2022 Sep 14]. Cardiovasc Drugs Ther. 2022;10.1007/s10557022-07379-z. doi:10.1007/s10557-022-07379-z

4 Singh RB, et al. (2007). Effect of coenzyme Q10 on risk of atherosclerosis in patients with recent myocardial infarction. Mol Cell Biochem. 297(1-2):21-30.

5 Bonnefont-Rousselot D. (2016). Resveratrol and cardiovascular diseases. Nutrients. 8(5):250.

6 Qian H, et al. (2016). The potential of black garlic (Allium sativum) for prevention of cardiovascular disease. Food Funct. 7(2): 833-844.

7 Ide N, et al. (2003). Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 69(5): 356-360.

8 Lee YM, et al. (2013). Black garlic (Allium sativum) extracts

9 Pittler MH, Schmidt K, Ernst E. Hawthorn extract for treating chronic heart failure: meta-analysis of randomized trials. Am J Med. 2003 Jun 1;114(8):665-74.

10 Walker AF, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn for patients with diabetes taking prescription drugs: a randomised controlled trial. Br J Gen Pract. 2006 Jun 1;56(527):437-43.

11 Walker AF, Marakis G, Simpson E, et al. Hypotensive effects of hawthorn extract: a randomized trial. Lancet. 2002 Jun 15;359 (9320):978-80.

12 Zick SM, Vautaw BM, Gillespie B, Aaronson KD. Hawthorn Extract Randomized Blinded Chronic Heart Failure (HERB CHF) trial. Eur J Heart Fail. 2009 Jun;11(6):990-9.

13 Cámara M, Fernández-Ruiz V, Sánchez-Mata MC, Cámara RM, Domínguez L, Sesso HD. Scientific Evidence of the Beneficial Effects of Tomato Products on Cardiovascular Disease and Platelet Aggregation. Front Nutr. 2022;9:849841. Published 2022 Mar 15. doi:10.3389/fnut.2022.849841

14 https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/j.efsa.2009.1101

15 Cámara M, Fernández-Ruiz V, Sánchez-Mata MC, Domínguez Díaz L, Kardinaal A, van Lieshout M. Evidence of antiplatelet aggregation effects from the consumption of tomato products, according to EFSA health claim requirements. Crit Rev Food Sci Nutr. 2020;60(9):1515-1522. doi:10.1080/10408398.2019.1577215

16 Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:6981. doi:10.1016/j.jep.2014.09.049

17 D'Angelo C, Franceschelli S, Quiles JL, Speranza L. Wide Biological Role of Hydroxytyrosol: Possible Therapeutic and Preventive Properties in Cardiovascular Diseases. Cells. 2020;9(9):1932. Published 2020 Aug 21. doi:10.3390/cells9091932