Cardiovascular support is a multipronged, and multi-ingredient, market.
Americans are sedentary. That’s a fact. More than 80 million Americans, ages six and older, are physically inactive.1 A more recent article from Forbes magazine2 stated that “the average American adult sits more than at any other time in history.”
And it’s not like we’re paying close attention to what we eat unless you’re counting those who watch as they wash down their oversized double cheeseburger with double gulps of sugary soda. Most of us take in way too many calories and go beyond the recommendations for sugar, sodium, and saturated fats.3 Obesity is pervasive, with government statistics indicating 42.8% of adults over the age of 60, 44.8% of middle-agers, and 40% of young adults aged 20-39 have the disease.4 That doesn’t even take into account the percentage of Americans who are simply overweight.
The statistics are sobering, especially when you consider that heart disease is still the leading cause of death in this country5 and that, in addition to genetics and smoking, poor diet and lack of exercise are among the contributors to heart disease. Genetics aside, this is a problem that’s preventable.
Where Do Supplements Fit In?
When it comes to heart health, pharmacist and author David J. Foreman sees the role of dietary supplement products focused on two areas: helping to prevent issues in the future and helping people work with their healthcare practitioners to reduce pharmaceutical dosages as a means of ameliorating the side effects of medications typically prescribed.
“These medications come with a price,” says Foreman, “and consumers don’t want to feel bad or have unwanted health outcomes due to their treatments. People are sick and tired of being sick and tired.”
Foreman, who is known as “The Herbal Pharmacist,” says in most cases “dietary supplements are not the full answer for many conditions such as heart rhythm or blood pressure” problems, but that doesn’t mean they shouldn’t have a role. In the case of other heart-related issues—using cholesterol or plaque buildup as examples—supplements can also be a preventative and can help reduce the risk of long-term damage, according to Foreman. He explains that “high cholesterol is not immediately life-threatening” and that for many people high cholesterol can be lowered in a relatively short amount of time through modifications in diet (including the right supplements) and exercise.
There are numerous supplements that are long associated with supporting heart health, including fiber, garlic, magnesium, CoQ10, red yeast rice, and omega-3 fatty acids. Foreman is particularly keen on omega-3s and is also excited about emerging research on vitamin K2, nattokinase, and black seed oil. (Full disclosure: Foreman is a consultant for TriNutra, an ingredient supplier of black seed oil.)
Early Research Suggests Nigella sativa May Support Healthy Blood Pressure
Nigella sativa is an annual flowering plant native to parts of Asia whose extracted black seed oil has been used for centuries to improve health, including lowering blood sugar and cholesterol levels. Thymoquinone, the main active constituent in black seeds, has antioxidant potential and is thought to be the most important component of black seeds.
Earlier this year, a non-randomized published human clinical study6 added to the research that suggests black seed oil also supports healthy blood pressure levels. The study followed 20 healthy patients for a 42-day (six week) treatment period, followed by a washout period of three weeks, then a placebo period for six weeks.
At baseline, the mean systolic blood pressure (SBP) value was 143.5 mm Hg (standard deviation (SD) = 12.6 mm Hg) and the mean diastolic blood pressure (DBP) value was 90.7 mm Hg (SD = 8.5 mm Hg). In the treatment phase, patients received 500 mg daily of TriNutra’s (Harrison, NY) trademarked ThymoQuin cold-pressed black seed oil, which is standardized to 3% thymoquinone.
During the six-week treatment period, subjects experienced a decrease of 11.2% in SBP and 12.2% in DBP. At the conclusion of the trial, after the six-week placebo phase, the mean SBP was 131.0 mm Hg (SD = 13.3 mm Hg) and the mean DBP was 77.9 mm Hg (SD = 12.1 mm Hg). The authors did note several study limitations, including a small study population and a short washout period.
According to Morris Zelkha, cofounder, TriNutra, “There are several studies supporting the functional claim that black seed oil helps to maintain a healthy blood pressure7, 8, 9.” He notes that the main differences between those other studies and the 2020 study was the time it took subjects to respond to supplementation and the different form of placebo. He says, “In our recent study, blood pressure began to drop starting two to four days after beginning to supplement with ThymoQuin. This is significantly better [compared] to the other recent studies, which showed benefits after two to three weeks.”
Further, Zelkha explains how the study accounted for the differences between subjects taking blood pressure medication in addition to being supplemented with black seed oil. All subjects who used blood pressure medication were separated from those who did not, and the results were then measured and reported as a whole group and as two separate groups, he says.
“While those without the medication had a more significant drop in blood pressure levels,” Zelkha says, “the patients under medication had a better response to the ThymoQuin during the washout period.” That being said, he believes there is a need for more studies that look into the effectiveness of his company’s ingredient in the context of drug interactions to better understand how the supplement and the drug work together.
Zelkha advises TriNutra intends to conduct additional studies on the potential blood pressure–lowering effect of its black seed oil ingredient. In fact, there is an additional study in process with results expected by the end of the year, he says.
Garlic, Carob Bean, and a Healthy Heart
According to folklore, garlic has mystical abilities to ward away evil spirits and vampires—or maybe that’s just because of garlic’s pungent odor, which by the way is also thought to repel snakes.
From a scientific standpoint, garlic has many uses for promoting good health, including its potential to reduce SBP and DBP in people with high blood pressure. Another heart-healthy benefit of garlic is its ability to reduce cholesterol and low-density lipoprotein (LDL) in people with high cholesterol levels—and although not all studies are in agreement in that area, garlic is generally recognized by nutritional experts as a tool to consider in the healthy-heart toolbox.
This past January, Pharmactive Biotech Products (Madrid, Spain) announced its launch of ABG10+, an aged black garlic extract for functional food applications (and the culinary market) that is standardized to a higher concentration of the water-soluble, bioactive compound S-allylcysteine (SAC) known for its antioxidant content and cardiovascular benefits.10
Pharmactive’s head of research and development, Alberto Espinel, PhD, advises a new human clinical study using his company’s garlic extract is close to completion. He says some preliminary results appear promising for the higher SAC content and cardiovascular health.
Espinel also points to the heart health benefits of carob powder. Carob powder is a baker’s delight, often substituting for chocolate because of its low glycemic index. Espinel reminds us that carob is actually an ancient and highly nutritious fruit, rich in polyphenols and prebiotic fibers.
Earlier this year, an animal study using Pharmactive’s branded carob bean extract, CSAT+, demonstrated the ingredient supported cardiometabolic health factors.11,12 The mice were fed a high-sucrose and high-fat diet and supplemented with CSAT+. Results showed a reduction of total cholesterol and LDL cholesterol. “The polyphenols, fibers, and antioxidants present in CSAT+ were able to reduce the accumulation in fat adipose tissue and reduce the LDL-cholesterol levels into those similar to a control diet,” Espinel states. The results were consistent with the findings from a previous, unpublished study that found supplementation with a carob bean extract supported obesity-induced endothelial function, he says.
Investing in science on carob extract is important to Pharmactive, says Espinel. “Whilst there is ample data on its biochemical profile, there exists a very limited number of clinical trials demonstrating the beneficial effects of carob extract on cardiovascular health.” He views the animal studies as positive and an indication to “mark the next step” towards a clinical investigation.
He adds, “Specifically with CSAT+, we are planning to invest in a human study to prove its comprehensive relationship with weight management. The progressive control of appetite allows a regulation of weight in the medium-/long-term, and both tend to often go hand-in-hand with metabolic disorders such as diabetes and heart and vascular disease.”
Increased Nitric Oxide Production Linked to Improved Circulation
Google “nitric oxide supplements,” and numerous choices pop up. But nitric oxide is not actually a supplement ingredient; it’s a chemical compound produced by our bodies which, among other things, has been found to be of importance to the cardiovascular system. The proper amount of nitric oxide production keeps blood vessels healthy, relaxing them to ease blood flow and help control blood pressure.
“We’ve educated consumers on the importance of preserving vascular health by increasing nitric oxide for many years, focusing on nutrients like pomegranate, resveratrol, and non-formulated arginine,” shares Michael A. Smith, MD, director of education and spokesperson for supplements brand Life Extension.
He adds, “The health benefits of nitric oxide are not new.” In fact, he advises, they’ve “been well known for many years. What is new is how we can help the body produce and preserve more of it through targeted supplementation.”
Life Extension offers numerous products to improve nitric oxide production, including a line in the heart health category. Earlier this year, Life Extension announced a new formulation13, NitroVasc Boost, delivered in on-the-go berry-flavored powder stick packs, that “represents a major leap forward in increasing nitric oxide production and improving its bioavailabilty,” says Smith.
According to the company’s press release, the new formula uses the “…innovative Nitrosigine, composed of bonded L-arginine, inositol, and silicon—a combination that allows it to stay in the bloodstream longer.” Nitrosigine bonded arginine silicate is a branded ingredient from Nutrition 21 (Purchase, NY).
A randomized, double-blind, active controlled, crossover study in a small population of healthy males, ages 18-40, showed that Nitrosigine significantly increased plasma arginine levels at multiple time points up to six hours post-dose in comparison to arginine hydrochloride (ArgHCI) supplementation which only showed the increase for one hour. The study authors further concluded that the Nitrosigine treatment resulted in a >70% increase in plasma arginine AUC (area under the curve) compared to ArgHCl, and showed a lower standard deviation than that seen with ArgHCl. This suggests, they advised, that Nitrosigine is a more bioavailable, and less variable, source of arginine.14
Life Extension’s NitroVasc Boost also includes 500 mg of the whole-fruit powder of chokeberry (Aronia melanocarpa), a rich source of polyphenol compounds that “encourage[s] endothelial nitric oxide synthase activity, the enzyme that promotes nitric oxide production,” the company says.
Speaking of chokeberry, also known as aronia berry, a study published last year in The American Journal of Clinical Nutrition examined the potential vascular benefits of aronia berry supplementation, studying both aronia berry whole-fruit and extract powder. Researchers also looked at any effects on the gut microbiota composition.
In the 12-week double-blind, placebo-controlled parallel designed study15 in 66 healthy men, subjects were randomly assigned to receive either a polyphenol-rich extract (116 mg, 75 g berries), a whole-fruit powder (12 mg, 10 g berries), or placebo for 12 weeks. The study authors concluded, “In healthy men, consumption of aronia berry (poly)phenols improved endothelial function and modulated gut microbiota composition, indicating that regular aronia consumption has the potential to maintain cardiovascular health in individuals at low risk of cardiovascular disease.”
Constructing Future Scientific Research
A new consumer survey funded by the Council for Responsible Nutrition (Washington, DC) and fielded by Ipsos found that nearly one-quarter (23%) of Americans take dietary supplements to support heart health.16 Clearly, there is an interest from consumers in these supplements.
Foreman has intriguing suggestions for future research studies. “I see a need for more research in humans who are currently under medical care and taking medications to see if the addition of certain dietary ingredients can improve their outcome and allow a lower dose of the medications to be used.” He explains that if the results of those trials demonstrated that certain dietary ingredients working in combination with lower doses of medication showed success, he believes quality of life would improve for those patients and, in turn, patient compliance would also improve.
Another idea? “The industry should look to combine clinically proven ingredients that improve health in other areas which are associated with heart disease, such as supporting the microbiome, weight control, and managing stress and sleep,” suggests Foreman. “An example would be combining an ingredient for stress with other ingredients which support healthy blood pressure. Since stress is an underlying cause of high blood pressure, we can help that consumer decrease stress and hopefully reduce their blood pressure at the same time.”
Sounds like a win-win all around. Healthy heart, happy life.
Pterostilbene May Influence the Gut Microbiome and Heart Health
Last year, Sabinsa Corp. (East Windsor, NJ) announced the results of an animal study1 on the company’s branded Silbinol pterostilbene ingredient with novel findings for heart health. Shaheen Majeed, the company’s worldwide president, advises that the results “clearly show that pterostilbene attenuates the level of trimethylamine-N-oxide by influencing gut microbiota composition (reducing the strains producing trimethylamine) and by reducing the levels of enzyme FMO3 in the liver.”
Pterostilbene, the active compound in Sabinsa’s Silbinol, is a di-methylated version of resveratrol, extracted from the heartwood of Pterocarpus marsupium, also known as the Indian kino tree, which is referenced in the traditional Ayurveda Indian system of medicine.
Previous studies2,3 on the compound demonstrated potential benefits in other areas, including the safety and immunomodulation potential in healthy human subjects in supporting immune health and supporting healthy blood sugar levels.
The most recent study in mice puts the company on the path toward better understanding the role the ingredient has in cardiovascular health. As Majeed puts it, “The present study is unique in that it is the first evaluation addressing the peculiar mechanism through which pterostilbene acts to regulate the cardiovascular pathology. Although pterostilbene has been investigated for its multiple pharmacological benefits across the globe, its influence on the trimethylamine-N-oxide and finally cardiovascular risk is assessed for the first time. The study evaluates and provides some crucial links to decipher the potential of pterostilbene in ameliorating cardiovascular risk.”
Trimethylamine-N-oxide has been accepted worldwide as a potential biomarker to assess the development of cardiovascular disease. It is a metabolite of the trimethylamine derived from choline metabolism. Trimethylamine-N-oxide is derived two ways: 1) by the action of intestinal microflora, and 2) by a liver enzyme, flavin-containing monooxygenase 3 (FMO3), on trimethylamine.
Majeed further advises that in addition to showing the effect on the microbiota composition, the study results “showed decreased levels of pro-inflammatory markers involved in vascular inflammation leading to cardiovascular disease progression, [including] tumor necrosis factor-(α) (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin.”
“Sabinsa is continuously working to validate the pharmacological potential and assess the safety of pterostilbene through preclinical and clinical evaluation. Various in-house preclinical evaluations involving cell lines, conducted in the Sami-Sabinsa Group’s research and development wing, have provided solid proof of the ability of pterostilbene to reduce cardiovascular risk,” says Majeed. “Based on the observations of preclinical experiments, the animal study was conceptualized to assess the same in vivo. The animal study outcome indicates great potential, which needs to be confirmed in other animal studies and human clinical trials.”
Majeed calls clinical trials “the gold standard to validate the targeted pharmacological benefit and safety of any bioactive, thus assuring its further usage in large populations. The results of the animal study are encouraging, and Sabinsa is working to evaluate and validate the cardio benefits of pterostilbene in human subjects.”