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Too Much Pressure


High blood pressure’s moniker “the silent killer” is no exaggeration. In 2009, it was estimated that almost 80 million Americans, or one in three adults, many of whom are unaware, have high blood pressure, which increases the risk for heart disease and stroke—the leading causes of death in America.

“Since heart disease and high blood pressure are so prevalent, the market for dietary supplements is significant, estimated to exceed $1.6 billion in sales,” said Jeremy A. Holt, manager of health services with Ajinomoto USA in New Jersey. “The factors contributing to this demand include aging Baby Boomers, people looking for natural alternatives to drug therapy and more health-conscious consumers.” 

Tanushree Bose, PhD, clinical development senior manager with Californiabased ChromaDex, Inc., added that the heart health market has surged over the past 10 years, also pointing to the aging of the Baby Boomer generation. “The Baby Boomers are the first generation that really stressed education and knowledge, and they are putting it to good use by researching new ways to maintain their health as they get older, said Bose, noting that during the recession, as health care costs rose and health benefits were cut, people started looking to nutraceuticals as an alternative and cheaper means of combating and preventing illnesses. “In short, I believe the broadness of the market is advantageous because our target audience is looking for nutraceuticals that pinpoint specific diseases (i.e., cholesterol, blood pressure, diabetes and atherosclerosis).” 

In addition, Dan Lifton, president of the proprietary branded ingredients division of New York-based Maypro Industries, said mainstream media coverage, such as The Dr. Oz Show, is growing consumer awareness about the side effects of statins. “We are bullish on the blood pressure segment. The prevalence of the condition is continuing to rise along with the growing rates of obesity and diabetes around the world, but it’s not an easy segment to reach since many consumers with high blood pressure are already on medication. So the target is a pre-hypertensive patient seeking to avoid going on drugs.” 

High blood pressure is prevalent for a number of reasons. For example, high rates of obesity, sedentary lifestyles and aging of the population are all contributing factors. And, according to an unpublished American Heart Association computation, projections show that by 2030 the prevalence of hypertension will increase 7.2 percent from 2013 estimates, noted Bose.

“With high blood pressure there is a Higher chance of heart attack, stroke, kidney diseases and heart failure,” he said, pointing to reports that mortality from both ischemic heart disease and stroke doubles for every 20 mmHg increase in systolic blood pressure, or 10 mmHg increase in diastolic blood pressure. “In the population, reducing systolic blood pressure by 5 mmHg will result in 14 percent reduction in mortality due to stroke, nine percent decline in mortality due to coronary heart disease and seven percent decrease in all-cause mortality.”1 

Ingredients of Interest 

Suppliers are focusing on antioxidant ingredients as well as ingredients with ACE-inhibiting properties. ACE inhibitors restrain angiotensin-converting enzyme (a component of the blood pressure-regulating renin-angiotensin system), thereby decreasing the tension of blood vessels and blood volume, thus lowering blood pressure.

Jeff Lind, vice president of the health business unit of Israel-based Frutarom (with U.S. offices in California and New Jersey), said the company’s primary ingredient for supporting a healthy heart and healthy blood pressure is Benolea®, an extract of olive leaf (Olea europa).

A randomized, double-blind study on 232 volunteers with stage-1 hypertension using Benolea demonstrated both its blood pressure reduction and lipidlowering effect, as well as the extract’s safety and tolerability. The efficacy of Benolea has been also demonstrated in vitro as an ACE inhibitor. “ACE inhibition is related to preventative effects on the modification of the vascular system,” Lind said, adding that olive leaf is also well regarded as an antioxidant, making Benolea an ideal all-around proven ingredient for cardiovascular health.

Maypro Industries recently launched its newest ingredient, AmealPeptide®, also an ACE inhibitor. “The product has been shown to work as effectively as a pharmaceutical with the same mode of action, but without the side effects,” Lifton said, noting that the compound was developed by one of the largest Japanese beverage companies and is FOSHU-registered with a health claim in Japan. “The human clinical data is very compelling. With the exit of some peptide- based products in the market, we believe that this ingredient is in the position to dominate the market and it is already used by about 10 brands in the industry.”

While fish oil, niacin, pantethine, walnuts and many other ingredients have been explored for arterial health, another option, according to Holt, is lactotripeptide (LTP).

Naturally derived from the milk protein casein, LTP consists of two tripeptides—valyl-prolyl-proline (VPP) and isoleucyl-prolyl-proline (IPP)—and is the dietary ingredient in Ajinomoto’s Natura Guard BP. “LTP promotes healthy blood pressure by inhibiting ACE, which contributes to blood vessel constriction,” he explained.

Dr. Matthew Budoff, professor of medicine at the David Geffen School of Medicine and director of cardiac CT, Harbor-UCLA Medical Center, in California, said that while no one ingredient is best for all individuals, many experts believe that antioxidants show great promise for reducing high blood pressure and supporting heart health. He said he is particularly excited about pterostilbene, the blueberry antioxidant, which is available as pTeroPure®, by ChromaDex.

“Many are aware of the grape antioxidant, resveratrol, but while both resveratrol and pterostilbene are stilbenes and belong to the same class of compounds, the structure of pterostilbene differs from resveratrol,” said ChromaDex’s Bose. “Pterostilbene has superior biological activity, better oral bioavailability and metabolizes more slowly in the body than other antioxidant polyphenols, allowing more time for its antioxidant activities to act.” 

Along with a number of other effects, pterostilbene has shown great promise for supporting cardiovascular health and cognitive function by activating “good” proteins such as PPARá which helps lower cholesterol levels, increases the expression of endothelial nitric oxide (a vasodilator) and increases expression of the antioxidant enzyme manganese superoxide dismutase in the brain, according to the company.

In addition, the independent research company Frost & Sullivan named the ingredient the 2010 North American “Most Promising Ingredient of the Year.” 

Daily Delivery 

Manufacturers and suppliers stress the importance of consistent dosing of natural products for heart health. To that end, Maypro Industries employs the Sustained Release technology in its MicroActive® CoQ10 product, said Lifton. “Controlled release is important in the case of CoQ10, which has clinical data showing it reduces blood pressure, since it’s important to sustain CoQ10 levels in the blood for 24 hours. While many consumers tend not to comply with divided dosages of two to three times a day, this product can be taken once a day and deliver a benefit over 24 hours, which is a big value add. Of course, there are also advantages related to improved bioavailability and universal absorption, i. e. eliminating inter-subject variance in uptake.” 

ChromaDex’s pTeroPure pterostilbene is lipophilic and has superior cellular uptake and a long half-life in the blood, according to Bose. “Most products in the market with pTeroPure pterostilbene incorporate the ingredient in a capsule. The most effective drug delivery formats for high blood pressure are oral drug delivery systems. PTeroPure has a high rate of absorption and reduced first-pass metabolism in the liver.”2 

“Any delivery system that likens the chance a consumer will ingest the supplement regularly and over an extended period of time (and/or appropriate for their condition) should be considered effective,” said Frutarom’s Lind. “It’s a supplier’s job to be familiar with delivery systems, but manufacturers need to ask themselves how they are engaging their customer once that box goes into the consumer’s cabinet. How can they optimize the supplier’s data in their marketing campaigns to promote consumer confidence, compliance and loyalty? In a nutshell: savvy marketing and social media.” 

The consumer’s willingness to remember to take their vitamins is certainly essential. In fact, Budoff said a combination of diet, exercise and supplements is where one begins for the treatment of those at risk. “Treatment of high blood pressure is life-long and the pressures tend to go up with age as the person’s arteries get stiffer,” he said. “Because of this, it is very important to find an approach that is both tolerable and agreeable to the patient. Many of my patients would prefer a more natural approach to treating their blood pressure elevations, so I try supplements and diet first, with an agreement that if our goals are not met, we will add a medication.” 

Research & Progress

While knowledge is said to lead to power, that often isn’t the case. “Despite the great strides in the understanding and treatment of cardiovascular disease, it continues to be the leading cause of death worldwide,” noted Bose. “The primary risk factors that contribute to cardiovascular disease are hyperlipidemia and hypertension.3 Foods and supplements that address these risk factors are a high priority.” 

He pointed out that numerous animal studies have shown the positive benefits of pterostilbene, and recently the first clinical trial evaluated its impact in humans. The double-blind, placebo-controlled, clinical trial, conducted by the University of Mississippi, enrolled 80 adults averaging 54 years of age with high cholesterol (total cholesterol of 200 or greater and/or LDL cholesterol of 100 or greater). Patients were randomized to receive either pTeroPure pterostilbene, with or without a grape extract, or placebo for a period of six to eight weeks. The effect of pTeroPure on blood pressure, body weight and cholesterol were assessed at the beginning and end of the trial.4

Data from the trial, presented in September 2012 at the American Heart Association’s High Blood Pressure Research 2012 Scientific Sessions, demonstrated that patients taking pTeroPure achieved significant reductions in blood pressure compared to placebo [7.8 mmHg in systolic BP (p < 0. 01) and 7.3 mmHg in diastolic BP (p <0. 001)]. The only change in lipids was an increase in LDL cholesterol with pTeroPure, which was less among participants on cholesterol-lowering medications and was not seen among those who also received a grape extract along with pTeroPure. Body weight did not change significantly with pTeroPure compared to placebo. Participants not on cholesterol-lowering medication also achieved a minor average reduction in body weight (reduced body mass index 0. 59 kg/m2) with pterostilbene over the course of the study.5 

Ajinomoto’s Natura Guard BP’s 12 clinical trials published between 1996 and 2005, including 623 participants, have demonstrated significant changes in both systolic and diastolic blood pressure. This evidence demonstrates the positive effect of the dietary ingredient lactotripeptide (LTP) on blood pressure.

“This is important since it is wellestablished that a decrease in systolic blood pressure (SBP) and diastolic blood pressure (DSP) of 5 mmHg can lead to a seven percent and 16 percent decrease in CVD incidence, respectively,” said Holt.

Clinical data in well-designed placebo- controlled studies are what manufacturers are seeking, Lifton explained. “Interestingly, blood pressure is subject to a placebo effect, so uncontrolled trials don’t prove efficacy. Design is very important. Understanding the mode of action is important as well, and of course, there is safety.”

Progress has come from innovative and research-driven suppliers, agreed Lind. “Suppliers are facing pressure from finished goods companies to deliver innovation, quality clinical data and to establish ingredients safety,” he said. “As a keener eye is trained on supplements by government agencies on a global level, the companies are turning to suppliers as their partners in delivering quality, safety and efficacy.” 

Budoff acknowledged that the attention to these qualities by the natural products industry is seeing a reward: the acceptance the complementary medicine field is garnering from traditional physicians is “remarkable.” “Even in the recent past, there weren’t any complementary or alternative medicine presentations at the mainstream cardiology meetings. Now, there is standing room only at the complementary sessions at all the national cardiology meetings,” he said, noting that at the meeting of the American College of Cardiology last year, he couldn’t even enter the room on the sessions related to complementary medicine, as they were brimming with cardiologists.

“Interest has never been higher, and this trend will continue,” Budoff added. “It is important to recognize that, for a long time, nutraceuticals had little or no research to back up claims, but now we see more companies demonstrating the benefits of their products in clinical trials.”


1 National Heart, Lung, and Blood Institute. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. August 2004. Accessed at www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf on December 20, 2012.

2 Kapetanovic IM, Muzzio M, Huang Z, Thompson TN, McCormick DL. Pharmacokinetics, oral bioavailability, and metabolic profile of resveratrol and its dimethylether analog, pterostilbene, in rats. Cancer Chemother Pharmacol. 2011; 68(3):593-601.

3 CDC. CDC Features: High Blood Pressure & Cholesterol: Out of Control in US. Updated January 2011. Accessed at www.cdc.gov/Features/Vitalsigns/ CardiovascularDisease/ on December 20, 2012.

4 Riche DM, Deschamp D, Griswold ME, McEwen CL Riche KD, Sherman JJ, Wofford MR. Impact of pterostilbene on metabolic parameters in humans. Poster presentation at: American Heart Association 2012 Scientific Sessions on High Blood Pressure Research, September 20, 2012.

5 Riche DM, Deschamp D, Griswold ME, McEwen CL Riche KD, Sherman JJ, Wofford MR. Impact of pterostilbene on metabolic parameters in humans. Poster presentation at: American Heart Association 2012 Scientific Sessions on High Blood Pressure Research, September 20, 2012.

Decreasing blood pressure risks with science-supported natural alternatives is gaining traction with consumers seeking to avoid “Big Pharma.” The first of NIE’s two-part heart health series.