Heart disease remains the world's biggest health threat. Here’s the latest on nutrition ingredients to help us care for the heart.

Nutritional Outlook, Nutritional Outlook Vol. 24 No. 9, Volume 24, Issue 9

Despite the attention on COVID-19, heart disease is still the number one killer. Can dietary supplements play a role in heart health?

Cardiovascular disease (CVD) remains the world’s number one killer, even as COVID-19 and its variant strains dominate front-page news. It’s a fact we can’t forget.

We can’t lose sight of the importance of heart health, even as consumers devote more attention to other health priorities during the pandemic, like immunity. “Truth is, right now,” says Annie Eng, CEO of ingredients supplier HP Ingredients (Bradenton, FL), “the key focus is on immune support—and rightfully so.”

The good news? The pandemic has made consumers increasingly aware of the risks associated with CVD, says Steven Riley, director of marketing and consumer sales for UK-based ingredients supplier OptiBiotix Health PLC. After all, he says, “We now know that clinical outcomes are worse in patients with COVID-19 that have cardiovascular disease risk factors, such as obesity, diabetes, and hypertension.”1

“Compared to the general population, people with cardiovascular disease were more than twice as likely to contract severe forms of COVID-19,” notes Dominik Mattern, vice president, marketing, Kappa Bioscience (Oslo, Norway). “Thromboembolism and microvascular thrombosis are common in severe COVID-19 cases, and a leading cause of death.”2

Pandemic or no pandemic, cardiovascular wellness remains very important to adults, especially those in middle-age hoping to stave off potentially devastating cardiac events. “According to the latest information from the World Heart Federation,” shares Riley, “there are 520 million people currently living with cardiovascular disease. As such, it remains the world’s number one killer, causing 19 million deaths per year, which is mainly from heart attacks and strokes.”3

Sam Michini, vice president of marketing and strategy, Deerland Probiotics & Enzymes (Kennesaw, GA), raises other reasons why middle-aged adults might focus more on cardiovascular health—such as when they have a parent, grandparent, aunt, or uncle who has experienced a heart attack or has a debilitating heart condition. “It shoots up the priority list when one suffers a cardiac incident, which tends to be a spontaneous devastating event.”

The “prevention mindset” motivates these people especially to seek the health insurance of cardio-support supplements, he says.

Marianne McDonagh, vice president of sales for Bioenergy Life Science (Ham Lake, MN), agrees. “Heart disease is the leading cause of death in the western world, largely due to culture and lifestyle, and conventional medicine has done very little to decrease these chronic illnesses with pharmaceutical applications and assorted procedures. This has created a surge and increased interest in dietary supplements to support and maintain heart health.”

The desire to take a more active role in shoring up heart health will only be further spurred by the pandemic, says Jonathan Jones, PhD, chief scientific officer for ingredients supplier Monteloeder (Spain). “There is a rising interest in health as a whole. During the past year and a half, many consumers have been under lockdowns, with some countries still in strict living conditions.” He notes that “this lack of mobility, together with an increase in stress-induced binge eating and drinking, has had a negative impact on our health. Now that the countries are starting to open up, consumers are looking to get back in shape, fast.”

Jones, for instance, is intrigued by how digital consumer wearables add to the interest in heart health for consumers, advising that products such as Apple Watch and Fitbit trackers “have been working hard in developing the technology to track heart health parameters” such as heart rate, ECG, etc. For Jones, beyond the pandemic, the accessibility of this technology has increased awareness among consumers—which, he says, “has had an impact on their need for heart health solutions.”

The Heart Health Business: Alive and Ticking

Ingredient suppliers serving the heart health supplements market are also enhancing their own solutions. In the past year, several ingredient companies took notable steps to further their cardiovascular portfolio.

In July of this year, Ingredients by Nature (IBN; Montclair, CA) acquired the Sytrinol brand from Lonza4, an ingredient said to provide powerful support for the heart by influencing healthy cholesterol levels, healthy LDL levels, and healthy triglyceride levels.5 IBN plans to explore the synergistic combination of Sytrinol with its clinically backed lemon flavonoid brand Eriomin, the latter studied for its role in prediabetes management. By coupling the ingredients, “the combo may have even greater potential for prediabetes management and cardiovascular support,” according to a company press release.6

Says Rob Brewster, president, IBN, “Sometimes we make the mistake of sticking an ingredient into a box, but by thinking outside that box, we realize the interconnectivity of the different systems that maintain good health.”

He adds, “Heart health ingredients are just like that. Yes, the primary purpose of Sytrinol is to help the heart and cardiovascular system, but in doing so, there are other challenges that can be addressed, too.”

As examples, Brewster points to the possibility of the combined ingredients potentially playing a role in immune health and weight management, two areas that are intertwined with heart health. “That is why we want to explore how Sytrinol combines with other ingredients, especially flavonoids, and to expand on existing science with new and innovative research,” he says.

According to Brewster, IBN is “still in the ideation process of this.” The company intends to “run some internal studies to make sure that this combo is viable and effective,” he says.

Brewster adds, “We are currently finishing up a very promising SHIME study on Eriomin and may follow up with one on Sytrinol to see how it influences the microbiome as well.” He promises to share more information when available, which he expects to be in 2022 at the earliest.

Meanwhile, HP Ingredients strengthened its bergamot supply chain with its June 2021 announcement that it had purchased a stake in the Italian company Herbal & Antioxidant Derivatives (H&AD). According to the press release, HP Ingredients has been the exclusive North American sales and marketing partner for H&AD’s Bergamonte ingredient, a full-spectrum bergamot extract, since 2008, and a major contributor to H&AD’s revenue. The press release further advised that HP Ingredients has been brought in as a shareholder, with Eng now serving as one of the four directors of H&AD.7

Eng is enthusiastic about the current science behind Bergamonte, including 12 published human clinical trials examining the beneficial role for the branded ingredient in heart health. She’s equally enthusiastic about the continuing research and development opportunities.

She envisions opportunities in those areas for other citrus ingredients as well, advising that “we are finding that more consumers and brands are strongly associating citrus with more than immune resilience.” In addition to bergamot, she says they are linking grapefruits, lemons, limes, and oranges with a host of other health benefits, including those for heart health.

On another front, OptiBiotix—and its subsidiary ProBiotix Health—continues its global expansion with several announced extensions of commercial agreements that will enable wider international distribution for several of its heart health–focused ingredients and products. According to company press releases, these include WellBiome, a functional fiber and mineral blend; and its branded line of finished product, CholBiome, which contains LPLDL, a patented probiotic strain.8,9 In September 2020, OptiBiotix launched what the company called “an innovative tri-layer tablet” branded as CholBiomeBP and positioned it as a blood pressure support product.10

According to Riley, while there are many dual-layered solutions available in the market today, tri-layered solutions remain highly innovative. He explains that the specialized technology used in the range of CholBiome products enables each of the three-to-four ingredients per product to work in synergy and be released at optimal times to increase overall effectiveness. In the case of CholBiomeBP, says Riley, “Thiamine and L-arginine are released immediately; then, approximately two hours after ingestion, our patented probiotic strain LPLDL is released. Between four and six hours after the tablet is consumed, the final layer releases with CoQ10,” ensuring that the active ingredients experience increased stability and survivability after ingestion.

The State of Science

Even as companies count on business deals to improve the fortunes of the heart health category, there is recognition that at the end of the day, science is the beating heart of what will move the industry forward.

Probiotics

Kaneka Probiotics (Pasadena, TX) saw positive results from a recent heart health study using its branded ingredient, Floradapt Cardio, a multi-strain probiotic formulation comprising three strains of Lactobacillus plantarum (CECT7527, CECT7528, and CECT7529). The 12-week randomized, double-blinded, placebo-controlled clinical trial was designed to evaluate the efficacy of red yeast rice (as 10 mg of monacolin K) combined with the three-strain probiotic. The study population consisted of 39 adults with total cholesterol of ≥200 mg/dL who were statin-naïve or had recently stopped statin treatment because of intolerance.11

The researchers concluded that “this combination of 10 mg of monacolin K and L. plantarum strains was well tolerated and achieved a statistically significant greater reduction in LDL-C and TC in the intervention group compared to the placebo, once adjusting for recent history of hypercholesterolemia treatment.”

The researchers further advised that this particular combination of L. plantarum strains was chosen because it had previously been shown to lower cholesterol in a randomized, placebo-controlled clinical trial12 as well as shown to have high bile salt hydrolase activity and good safety data.11

The significance of bile in the cholesterol equation is “the primary mechanism behind probiotics for heart health,” Shastri believes. He explains that “it’s not commonly known that only about 15%-30% of circulating cholesterol comes from the diet. The rest is synthesized by the liver or recirculated in our bile salts.”

According to Shastri, Floradapt Cardio deconjugates bile salts into bile acids, rendering the bile acids less soluble and thereby increasing the excretion of cholesterol.

AB-Biotics, a Kaneka group company, funded the study11, supplied the probiotic strains, and was involved in data analysis.

A clinical study13, published in November 2020, demonstrated the efficacy of Deerland Probiotics & Enzymes’ branded probiotic Bacillus subtilis DE111 in promoting healthy endothelial function and supporting healthy cholesterol levels, according to the company’s press release.14

Specifically, the research team found that B. subtilis DE111 supplementation of 1 billion CFU per day resulted in significant reduction in total cholesterol and non-HDL cholesterol relative to baseline measures. The team also observed a strong trend toward reduction in LDL cholesterol as well as improvement in endothelial function. It also saw reactive hyperemia index (RHI), an indicator of blood flow and heart health, increase by 9.14%.14

“There are several studies showing the effect of other probiotics on heart health,” says John Deaton, PhD, Deerland’s vice president of science and technology. However, he says, “Our study shows a heart benefit from an inherently stable spore-forming probiotic that is resistant to most manufacturing and storage stressors.”

“Further,” he adds, “the study clarifies a clear ‘beyond digestion’ health benefit that can be conferred by a spore-forming probiotic strain. This is important in defining the health benefits of B. subtilis DE111 to enable consumers to know more about the differences between strains and which to turn to for the specific functional categories they are interested in.”

Kaneka also has consumers in mind. Shastri points out that while “probiotic applications for cardiovascular health are still in the early adopter stage,” he has seen research indicating that there’s a large gap between the number of people searching for probiotics for cardiovascular health and the number of probiotic products available on the market to support heart health. He shares that according to market research from Lumina Intelligence, during the 2017-2020 time frame, there were only 14 probiotic finished products marketed for cardiovascular health in the U.S., despite what he calls a “dramatic 1146% increase” during the same time frame in online searches and product reviews from U.S. consumers for that category.15

D-ribose and Ubiquinol

Published research, funded by the National Institutes of Health, National Institute on Aging, and the Department of Health and Human Services in the U.S., reviewed the role of mitochondrial metabolism as it may relate to HFpEF pathophysiology—and the potential mechanisms by which dietary ingredients ubiquinol and D-ribose may impact mitochondrial function. This news was shared by Bioenergy Life Science, which supplies a branded D-ribose ingredient, Bioenergy Ribose.16

In the paper, the researchers stated: “HFpEF is a common and often debilitating disease process that may be difficult to diagnose and has limited targeted therapeutic options. Mitochondrial dysfunction appears to play a significant role in the pathophysiologic processes of this clinical syndrome. Improved methods of diagnosis for HFpEF are needed, as are specific effective therapies. Active ongoing research into the roles of ubiquinol and D-ribose in HFpEF may provide clinicians with additional management opportunities.”17

The researchers noted that in their current clinical trial, they “believe supplemental oral D-ribose provides patients with HFpEF the extra substrate to bypass the G6PDH step and potentially increase the myocardial ATP levels. Though we are unable to measure myocardial ATP levels directly, we are obtaining blood ATP measurements in HFpEF patients receiving 15 g of D-ribose or placebo over 12 weeks. Since this current blinded study is still in progress, we are unable to report these data, but we will have a more in-depth metabolic explanation after study completion.”17 The study was projected to conclude in March 2021 but results were not shared by the time this article was written.

More cardiovascular science is in the works for Bioenergy Life Science’s ingredients, McDonagh says. “We are currently studying both Bioenergy Ribose and RiaGev for new parameters within the heart health category.”

Vitamins

Kappa Bioscience, known for its pure, all-trans vitamin K2 MK-7 ingredient, faces an interesting challenge. Vitamin K has been around for a very long time, but despite the vitamin’s longevity, Kappa Bioscience’s Mattern says that not only consumers, but even the industry, tend to overlook vitamin K.

But, he says, “What could be seen as a challenge might actually be an opportunity, as many still do not know about the difference between vitamins K1 and K2, their roles, and how this impacts their health benefits.”

From a dietary supplement perspective, for instance, vitamin K2 has been shown to make vitamin D3 products better, safer, and more effective, Mattern says. He adds that “this is new news to many, including [healthcare] practitioners. More benefit awareness for K2 will highly influence consumer purchasing behavior. Consequently, investment into communication and education is needed; that is a true and valid recipe for every trailblazer in the ingredient business.”

Part of that recipe also includes an ongoing commitment to science. According to Trygve Bergeland, PhD, vice president, science, Kappa Bioscience, “Two of Kappa Bioscience’s research partners are working on clinical trials in the cardiovascular health area using our K2VITAL pure all-trans vitamin K2 MK-7. Both of the [trials are] assessing arterial calcification reduction and potential cardiovascular parameters improvement thanks to supplementation.”

More specifically, Bergeland advises, “In the AVADEC trial, supervised by a research team from the Odense University Hospital, in Denmark, the last participant finalized the study in early 2021, and now an extensive analysis is ongoing.” He notes that the study population consisted of 400 patients diagnosed with aortic valve calcification.

The InterVitaminK trial, planned by the Frederiksberg Hospital, also in Denmark, has similar objectives, but is looking at a healthy population of 450. Inclusion is about to start, and the trial is expected to take three years. Bergeland says the protocol for this randomized controlled trial was presented in September at the International Vitamin Conference in Copenhagen.

“After being overlooked by scientists for decades,” says Bergeland, “vitamin K2 is coming back under their radar, as many areas are still to be explored.”

Botanicals

HP Ingredients’ Eng advises that her company’s LJ100 tongkat ali (Eurycoma longifolia) was shown in a recently published study to improve cardiorespiratory fitness in men with androgen deficiency (ADAM). In the study, 45 men took either LJ100 or placebo for six months while concurrently working out. Those taking the supplement experienced an approximately 10% greater reduction in ADAM symptoms than those in the placebo and workout group.18

Monteloeder has science news, too. According to a company press release, a randomized, double-blind, placebo-controlled study published in spring 2021 demonstrated that daily consumption of the company’s proprietary Metabolaid branded botanical extract ingredient was able to significantly reduce blood pressure. The most remarkable results were observed in the daytime measurements—particularly in systolic blood pressure, which showed a decrease of 5%. The study was conducted in a population of 80 unmedicated, slightly hypertensive subjects over an 84-day period.19,20

There’s more to come, says Jones. “We are currently working on analyzing the effect of combining our branded ingredients with a mobile app that helps manage consumer behavior towards a healthy lifestyle. The most relevant outcomes in this study are weight loss and blood pressure,” he says.

Why Fund Science?

There’s no question that supporting science through research grants or supplying ingredients or involvement in proper study design can go a long way for ingredient suppliers and finished product manufacturers. Not to mention consumers.

But what about the critics, those who prefer not to see any involvement from industry?

According to Deerland’s Deaton, “Some would argue that industry funding of scientific studies introduces bias, but this isn’t always the case, and ethical suppliers know how to ensure bias is not introduced. There are ways to prevent bias in supplier-funded research via the introduction of protective check points.”

He refers specifically to the recent cardiovascular health study13 for which Deerland not only supplied the ingredients and study funding but also collaborated with the university on the study design protocol as an example of how to do things properly.

Deaton says protection from bias was in place via the fact that the university performing the study was independent from his company. The statisticians analyzing the data were also independent, and the study was approved by an independent Institutional Review Board (IRB) that received no financial compensation.

He adds that “the study was also double-blinded to prevent the researchers from knowing who was receiving the placebo or the probiotic treatment. The final checkpoint in place was that the findings of the study were written by the university researchers and then submitted to a scientific journal that requires review from experts [before publication] that were in no way affiliated with the study or our company.”

Deaton emphasizes that “as long as check points like these are in place, then the quality and validity of industry-funded studies can be on par with those that rely on other sources of funding.”

And, he concludes, as long as companies use protective checkpoints to prevent bias, “it is good and helpful for them to financially support science.” After all, unlike well-funded drug studies, nutraceutical research often needs an additional boost. “This support helps promote applied research directly relating to consumer health needs that may not otherwise occur. It also helps ensure that products available to consumers, and the claims used to market them, are backed by valid science,” he says.

Monteloeder’s Jones is also a proponent of industry support for science. “Funding science is vital in order to advance in the field,” he says. “This is the same situation that exists in clinical research for Alzheimer’s disease, cancer, or any other major disease. Without private funding, we would not have the current knowledge nor available treatments that exist today.”

“In addition,” he says, “an important part of our funding comes from public grants; therefore, these studies have been previously analyzed by scientific experts and validated by public authorities. Furthermore, all our studies are published in peer-reviewed journals, and we ensure to make them available for anyone to read.”

According to Jones, Monteloeder provided the ingredients and participated in the study design and interpretation of the results of the aforementioned study.19(19) His company also provided funding, as did several national and international public organizations, including the Horizon 2020 project from the European Union.

“Science is part of our DNA,” he says, “so for us, having a deep knowledge of our botanicals, from the raw materials to extraction process, formulations, mechanisms of actions, and clinical efficiency, are of utmost importance.”

Bioenergy Life Science’s McDonagh also disagrees with the criticism of industry involvement, stating that “we advocate for all new research, even when funded by independent companies or universities, because research often reveals new awareness and discoveries. Additionally, by funding primary research using our branded ingredients, we can validate the ability of our specific ingredients, versus commodity brands, to deliver scientific benefits.”

Company-funded research also enables a company to demonstrate safety and efficacy for consumers. “Ethically speaking,” she says, “all researchers must disclose their conflicts of interest while drafting the manuscript for publication, and if this is done properly, there is no basis for a Catch-22 situation.”

Hope for Recovery?

Investing in science will also secure the long-term health and growth of the heart health category. As of now, the category could use it.

Brewster of Ingredients by Nature refers to market research from Nutrition Business Journal (NBJ) showing that while 2020 saw slightly better growth in the heart health category than in 2019, the category is expected to experience slower growth in 2021 and 2022—5.9 percent% and 3.6%, respectively21—because the pandemic caused most attention to shift to immune health.

And Deerland’s Michini paints a similar picture. He says NBJ’s annual Condition Specific Report projects heart health supplements to grow at an estimated rate of only 1.5% in 2023, which, he says, NBJ characterizes as “the worst growth year in the category in recent memory.”

“It’s an interesting challenge,” says Brewster, “because the health risks from the pandemic are made worse for consumers with preexisting cardiovascular challenges, but most consumers are focused more on short-term changes than looking at the big picture. This means it is important to develop products that fit into certain lifestyle scenarios that they can feel comfortable incorporating now that will also benefit them farther down the road.”

“One way to do this,” he advises, “is to figure out how to make heart health ingredients cross over into other areas as well. If we look at heart health from a more holistic sense, it may help to improve the situation. For example, we know that there is a connection between unhealthy blood glucose levels and unhealthy cholesterol, so by catering to consumers looking for improved blood sugar support, we can also help them with their heart health.”

“There are other categories that heart health ingredients can help with, too,” Brewster adds. “It just takes approaching the category from a new angle.”

Probiotics is one of those. Speaking about probiotics as an emerging heart health ingredient, Deerland’s Michini advises that probiotics are a vastly encompassing supplement category and, as such, require more specificity. “It has more marketable strains than the vitamin/mineral category has; therefore, it is essential to distinguish the powers of each strain and/or species. This would entail thoughtful positioning by brand marketers and, in turn, educated retailers.”

Kaneka’s Shastri advises consumers not to expect that by simply taking a probiotic, or any other nutrient for that matter, that a cardiovascular benefit will result. He believes consumer expectations should be modulated by the published science for that given effect on a particular nutrient.

In the case of probiotics, in order for there to be a benefit, “first the strains have to demonstrate a hypolipidemic effect in a randomized, placebo-controlled setting, and second, the finished product needs to have the identical potency as seen in the clinical trial,” he points out. Shastri says that’s the case with his company’s three-strain probiotic and another reason why Kaneka believes having sound science behind ingredients is vital to the category’s growth.12

And then, of course, there is the issue of communicating the benefits to consumers under a regulatory framework for supplements that doesn’t reward results from clinical trials with relevant claims.

Monteloeder’s Jones has some experience with that challenge. He says, “Product labeling is a balancing act to send the right message that resonates with the consumers while complying with the norms defined by the regulatory agencies.”

He understands why that’s important. “While this may seem unfair at first, especially if the claims are backed by solid science, it is important to maintain a strict level of contingency of what can be placed on a label. This increases consumer trust in the products in the market, as they are ensured that the claim complies with FDA/FTC regulations,” he says.

Jones reminds the industry that “there are many examples in the past where non-based claims have been applied to products that have turned out to be false, losing consumer trust that can ultimately affect the industry as a whole.”

But Jones does have one regulatory wish that results from a marketplace reality.

“On the other hand,” he says, “the nutraceutical landscape is a fast-shifting market strongly based on innovation, focused on consumer needs, in almost real time. Unfortunately, the regulatory bodies do not move at the same speed. Therefore, the industry as a whole would greatly benefit from a more agile regulatory body allowing faster innovations to appear in the market—of course, always considering consumer safety above all else.”

Riley of OptiBiotix agrees that there can be challenges when selling a product that does not have approved health claims. He also points to the challenges of differing country and continent regulations for quality, efficacy, and safety regulations. “Since regulatory frameworks can change from time to time, manufacturers and distributors must keep abreast of the different regulations to market their products effectively,” he states.

But Riley remains optimistic. “By using our collective scientific knowledge and combining it with the advancements in technology, we can make a significant difference in people’s lives, therefore decreasing the burden on global medical establishments and improving quality of life,” he says.

Mattern, of Kappa Bioscience, points to more reasons to be optimistic, citing insights from a recent report published by FMCG Gurus surveying tens of thousands of consumers worldwide. For example, he says, the report shares that “three in four consumers in North America plan to improve their heart health over the next twelve months,” and “56% regularly research about ingredients that can improve their health.”22

HP Ingredients’ Eng has an interesting twist on marketing the category. “Find ways to ‘reinvent’ what heart health means,” she says. “Get it out of the ‘for older folks only’ category and reinvigorate it for younger, healthy adults who want to remain physically vivacious.”

“Looking into the future,” says Eng, “as the Millennial generation enters middle-age, we see a great resurgence in focus on cardiovascular wellness but beyond choosing fish oils or CoQ10 for cholesterol management. This generation has been raised with the understanding that a healthy lifestyle can and will pay dividends for their well-being in the future; they self-educate and purchase supplements routinely. Cardiovascular health is integral to overall fitness, and this understanding is very strong with the younger generations.”

“For consumers, it’s not only about finding a dietary supplement that can aid their cardiovascular health,” says Riley. “It’s about discovering one that can effectively reduce their cardiovascular risk, either now or in the future.”

References

  1. Chung MK et al. “COVID-19 and cardiovascular disease.” Circulation Research, vol. 128, no. 8 (April 16, 2021): 1214-1236
  2. Janssen LHC et al. “Does the COVID-19 pandemic impact parents’ and adolescents’ well-being? An EMA-study on daily affect and parenting.” PLOS One. Published online October 16, 2020.
  3. British Heart Foundation. July 2021
  4. Grebow J. “Ingredients by Nature Acquires Sytrinol Heart Health Ingredient from Lonza.” Nutritional Outlook. Published online July 28, 2021.
  5. Roza JM et al. “Effect of citrus flavonoids and tocotrienols on serum cholesterol levels in hypercholesterolemic subjects.” Alternative Therapies in Health and Medicine, vol. 13, no. 6 (Nov-Dec 2007): 44-48
  6. Press release. “Ingredients by Nature Acquires the Sytrinol Brand.” www.ingredientsbynature.com. Posted July 23, 2021.
  7. Press Release. “HP Ingredients Solidifies, Strengthens Bergamot Supply Chain.” https://hpingredients.com. Posted June 25, 2021.
  8. Press Release. “OptiBiotix Announces Extension of Commercial Terms for Wellbiome & Cholbiome with Global Partners.” www.optibiotix.com. Posted August 5, 2020.
  9. Press Release. “Probiotix Health Expands in North America with Genuine Health Partnership.” www.optibiotix.com. Posted January 13, 2021.
  10. Marrapodi A. “ProBiotix Health Launches CholBiomeBP for Blood Pressure Support.” Nutritional Outlook. Published online September 10, 2020.
  11. Guerrero-Bonmatty R et al. “A combination of Lactoplantibacillus plantarum strains CECT7527, CECT7528, and CECT7529 plus monacolin K reduces blood cholesterol: Results from a randomized, double-blind, placebo-controlled study.” Nutrients, vol. 13, no. 4 (April 6, 2021): 1206
  12. Fuentes MC et al. “ A randomized clinical trial evaluating a proprietary mixture of Lactobacillus plantarum strains for lowering cholesterol.” Mediterranean Journal of Nutrition and Metabolism, vol. 9, no. 2 (November 25, 2016): 125-135
  13. Trotter RE et al. “Bacillus subtilis DE111 intake may improve blood lipids and endothelial function in healthy adults.” Beneficial Microbes, vol. 11, no. 7 (November 15, 2020): 621-630
  14. Press Release. “New Study: Probiotic DE111 Found to Support Cardiovascular Health.” www.deerland.com. Posted November 13, 2020.
  15. Lumina Intelligence report. “Probiotics, December 2020: Health Benefits Analysis Report.”
  16. Press Release. “Published Research Concludes that D-ribose and Ubiquinol May Be Useful in Helping to Manage Heart Failure.” Posted July 2020.
  17. Pierce JD et al. “Potential use of ubiquinol and D-ribose in patients with heart failure with preserved ejection fraction.” Annals of Medicine & Surgery. Published online May 18, 2020.
  18. Leitao AE et al. “Exercise associated or not to the intake of Eurycoma longifolia improves strength and cardiorespiratory fitness in men with androgen deficiency.” Complementary Therapies in Clinical Practice. Published online January 5, 2021.
  19. Marhuenda J et al. “A randomized, double-blind, placebo-controlled trial to determine the effectiveness of a polyphenolic extract (Hibiscus sabdariffa and Lippia citriodora) for reducing blood pressure in prehypertensive and type 1 hypertensive subjects.” Molecules, vol. 26, no. 6 (March 22, 2021): 1783
  20. Press Release. “Monteloeder Announces New Study that Demonstrates Its Metabolaid Extract Is Effective in Significantly Reducing Blood Pressure.” Posted October 13, 2021.
  21. Nutrition Business Journal. 2020 Condition Specific Report” and “2021 Condition Specific Report
  22. FMCG Gurus data. June 2021