Heart health ingredients, from land to sea

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More than half a million people in the United States die of heart disease every year, according to the Centers for Disease Control and Prevention. Heart disease causes one in four deaths; it is the leading cause of death for both men and women.

It’s no surprise, then, that supplements for cardiovascular health remain popular. CoQ10, reported on by Nutritional Outlook last year, continues to be in high demand and in good standing among physicians, consumers, and media outlets alike. Fish oil and other omega-3 fatty acid sources are ubiquitous on retail shelves and in online marketplaces, and ranked second among the most popular supplements in the United States in 2017 by Consumerlab.com. Fiber, garlic, and flaxseed are also universally known and commonly associated with cardiovascular wellness.

What follows is an overview of a variety of on-trend heart health ingredients-from the big household names to the smaller and more obscure-and the scientific studies that are advancing our knowledge of them.

Omega-3 Fatty Acids

EPA and DHA. As ingredients for promoting cardiovascular health, omega-3 fatty acids have been the subject of many years of research and considerable debate. Recent meta-analyses and a systematic review reach various conclusions, furthering the ambiguity.

In one meta-analysis¹, published by JAMA Cardiology in January 2018, the authors found a “non-statistically significant 7% reduction in CHD risk” with EPA and DHA supplementation. In another meta-analysis², published in the Journal of Clinical Lipidology and funded by omega-3 trade group the Global Organization for EPA and DHA Omega-3s (GOED; Salt Lake City, UT) in 2017, the authors found an 8% statistically significant reduction in cardiac death risk as a primary outcome overall, and “an even greater risk reduction, 17%, in those with high LDL or triglycerides,” Chris Gearheart, GOED’s director of member communications and engagement, explains. The greatest reduction in cardiac death rates-an almost 30% risk reduction-was observed in trials that utilized dosages of more than 1 g of EPA and DHA per day.

To help clear up confusion and better summarize the state of the science, Gearheart points to a GOED-commissioned editorial written by Kevin C. Maki (author of the GOED-funded Journal of Clinical Lipidology meta-analysis) and Mary R. Dicklin that explores the reasons behind the conflicting conclusions on the ingredients in question-and implications for future studies. Published this past July in Nutrients³, the piece by Maki and Dicklin states, “Although randomized clinical trial data accumulated to date have failed to provide unequivocal evidence of CVD risk reduction with long-chain omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation, many studies were limited by design issues, including low dosage, no assessment of n-3 status, and absence of a clear biological target or pathophysiologic hypothesis for the intervention.” The authors add that, in their analysis, the “most promising” evidence supports long-chain omega-3 polyunsaturated fatty acid supplementation for prevention of cardiac death.

Gearheart adds that since the beginning of 2017, GOED has been focused on commissioning research on omega-3s and heart health “to fill in the research gaps” and “continue to strengthen the body of science around” omega-3s. To this end, Gearheart says, results from two large randomized clinical trials on EPA and DHA and heart health will be enlightening. One is the Reduction of Cardiovascular Event Outcomes (REDUCE-IT) trial, which includes more than 8,000 subjects and was expected to determine whether Amarin Corp.’s EPA omega-3-based drug, Vascepa, makes an efficient add-on-treatment for patients already on statin therapy. In September, Amarin released topline results from the REDUCE-IT trial, stating that researchers found a statistically significant risk reduction of 25% in the first occurrence of major adverse cardiovascular events in subjects taking 4 g/day of Vascepa, compared to placebo. Amarin said it would release more details from the results at the 2018 Scientific Sessions of the American Heart Association in November.

The second trial whose results could support the promise of omega-3s in the heart health realm is the Vitamin D and Omega-3 Trial (VITAL), which follows 25,000 subjects, is sponsored by Brigham and Women’s Hospital, and is intended to measure whether taking vitamin D supplements or omega-3s reduces the risk of developing cancer, heart disease, or stroke in healthy people. Gearheart says GOED expects that the results of the VITAL trial will be positive; however, he expresses concern that the possibility of neutral or “not statistically significant” results could “result in headlines that inaccurately portray omega-3s as not effective,” which have plagued the industry in the past.

ALA and SDA. While much of the recent research and meta-analyses on omega-3 fatty acids have centered on DHA and EPA from marine sources, a review published this past July in Cochrane Database of Systemic Reviews examined trials that included plant-sourced omega-3 fatty acids as well.⁴

Nena Dockery, technical services manager for Stratum Nutrition (Carthage, MO), supplier of plant-based Ahiflower oil, calls the Cochrane review “significant in that it revealed a more promising effect from [omega-3] alpha-linolenic acid (ALA) consumption in reducing cardiovascular events, coronary mortality, and heart arrhythmia compared to EPA and DHA supplementation or fatty-fish consumption.”

Stratum’s Ahiflower oil, from the ahiflower plant (Buglossoides arvensis), contains omega-3 ALA, plus stearidonic acid (SDA), the “beneficial omega-6 fatty acid gamma linolenic acid,” and the omega-9 fatty acid oleic acid, Dockery says. She adds that the Ahiflower product is “unique in its content of SDA that converts much more readily in the body to EPA than does ALA, increasing the benefits associated with EPA above that from other plant sources.”

(Editor’s note: Some in the omega-3 industry have questioned the conclusions of the aforementioned Cochrane review. In Nutritional Outlook’s October 2018 issue, Bill Harris, PhD, omega-3 researcher and founder of OmegaQuant, bylined an article titled “Deep Dive” criticizing the Cochrane researchers.)

Plant Sterols

Plant sterols represent another plant-sourced ingredient marketed for cardiovascular wellness. Cargill’s (Minneapolis) plant sterols, branded within its CoroWise line of ingredients, are concentrated forms of plant compounds that can be formulated into foods and beverages as a “convenient way for consumers to try to help improve their LDL cholesterol levels and reduce their risk of heart disease,” says Pam Stauffer, global marketing programs manager for Cargill.

Stauffer says plant sterols are clinically shown to lower cholesterol and are recommended by the National Cholesterol Education Program of the National Heart, Lung, and Blood Institute of the National Institutes for Health. Stauffer points to two Frost & Sullivan reports to support her assertions: Small Prevention: Health Care Cost Savings and Supplements⁵, published in 2014, and the more recent Healthcare Cost Savings of Phytosterol Food Supplements in the European Union⁶, commissioned by Food Supplements Europe and published in 2017. The former maintains that between the years 2013 and 2020, nearly 2.3 million medical events could be avoided in American adults older than 55 with coronary heart disease through supplementation of plant sterols at preventative intake levels.  The report was funded by the dietary supplement association the Council for Responsible Nutrition (Washington, DC).

The latter report found that daily consumption of 1.7 g of plant sterols by adults older than 55 in the EU with severe high cholesterol could provide healthcare savings of €5.3 billion per year and prevent more than 170,000 hospitalizations, according to Cargill’s Alex Eapen, principal scientist.

Tocotrienol: The Other “E”

“The emerging trend in the vitamin E market” is how American River Nutrition’s (Hadley, MA) Anne Trias, MS, characterizes the ingredient tocotrienol. This form of vitamin E has been shown to safely lower cholesterol and triglyceride levels by 15%-20%, Trias says, while also reducing C-reactive protein-a measure of inflammation-by up to 40%. Additionally, a recent study⁷ published in The Turkish Journal of Gastroenterology elucidates the ingredient’s benefits in reducing cardiometabolic symptoms, improving fatty-liver index, and lowering body weight and inflammatory markers.

“There is still a gap in consumers’ understanding of the differences between vitamin E tocopherols and tocotrienols,” Trias says, “but many realize that the old picture that paints alpha-tocopherol as the universal and only vitamin E…is fading. Overall, tocotrienol is clearly the emerging trend in the vitamin E market, and we will be seeing a significant amount of research published in the next few years, adding to the growing body of science supporting this important ingredient.”

Resveratrol

The substance resveratrol has experienced upswings and downswings during the past 15 years or so. Resveratrol supplier Evolva (Reinach, Switzerland), however, says that the ingredient still supports normal blood pressure, reduces “the plasma total cholesterol level and the risk of arteriosclerosis,” activates endogenous antioxidant defense mechanisms, reduces inflammation, and more, according to Johannes Haerle, Evolva’s senior technical manager, commercial, and Gene Adamski, national sales manager.

“A very recent review and meta-analysis study summarizing resveratrol and its beneficial effect on cardiovascular disease was published in January of this year in Food Science and Nutrition,” Evolva’s Adamski says. The meta-analysis⁸ referred to resveratrol as a “nutraceutical” and concluded that “the favorable effect of resveratrol emerging from the current meta-analysis suggests [its possible use] as an active compound in order to promote cardiovascular health, mostly when used in [a] high daily dose (≥300 mg/day) and in diabetic patients.”

Ingredient supplier TR Nutritionals (Alpharetta, GA) also supplies resveratrol, and Deanne Dolnick, science director at the company, describes resveratrol as a “very popular” heart health ingredient at the company. TR Nutritionals offers “100% natural” resveratrol 50% and resveratrol 98%, she says.

High-Curcuminoids Turmeric Extract

TR Nutritionals calls high-curcuminoids turmeric extract “one of the newer ingredients to support heart health,” and cites a recent meta-analysis of randomized controlled trials published in 2017 in Nutrition Journal.⁹ Those researchers concluded in their analysis of seven eligible studies that turmeric and curcumin “may protect patients at risk of cardiovascular disease through improving serum lipid levels.” However, links between heart health and curcumin need more investigating, with the researchers concluding that additional research is required to resolve uncertainties related to dosage form, dose, and more.

Tomato Carotenoids

Tomato carotenoids, such as lycopene, have been “extensively researched and proven to beneficially modulate many of the key factors involved in cardiometabolic well-being and overall health over time,” says Karin Hermoni, PhD, head of science and nutrition at Lycored (Secaucus, NJ). The company has recently launched its second-generation tomato-carotenoid product, a “cardio-optimized” and “strictly standardized” tomato-nutrient complex called Cardiomato. The complex combines lycopene, vitamin E, and phytosterols in a proprietary formula whose clinical studies the company says provide evidence for the support of heart and cardiovascular health via healthy circulation, healthy blood pressure, and “boosting the body’s own protection mechanisms” against oxidative stress.

In October 2016, researchers published a study¹⁰ backed by Lycored of 150 subjects taking a carotenoid-rich tomato extract (CRTE) supplement daily after a meal. Overall, the results of this study indicate that CRTE taken once daily for two weeks has a favorable effect on postprandial LDL oxidation, glucose, insulin, and triglyceride levels for up to eight hours. CRTE was well tolerated throughout the study period, the authors write, “and additional trials are needed to prove the repeatability of these results in other sub-populations, such as those at risk of cardiovascular diseases.”

References:

1. Aung T et al. “Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77,917 individuals.” JAMA Cardiology, vol. 3 no. 3 (March 2018): 225-233
2. Maki K et al. “Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: an updated meta-analysis and review of research gaps.” Journal of Clinical Lipidology, vol. 11, no. 5 (September-October 2017): 1152-1160
3. Maki K and Dicklin M. “Omega-3 fatty acid supplementation and cardiovascular disease risk: glass half full or time to nail the coffin shut?” Nutrients, vol. 10, no. 7 (July 2018): 864
4. Abdelhamid A et al. “Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease.” Cochrane Database of Systematic Reviews, no. 7 (July 2018): 334-337
5. Frost & Sullivan and Council for Responsible Nutrition. “Smart Prevention: Health Care Cost Savings Resulting from the Targeted Use of Dietary Supplements.” 2014.
6. Frost & Sullivan and Food Supplements Europe. “Healthcare Cost Savings of Phytosterol Food Supplements in the European Union.” Brussels, Belgium: March 2017.
7. Pervez MA et al. “Effects of delta-tocotrienol supplementation on liver enzymes, inflammation, oxidative stress and hepatic steatosis in patients with nonalcoholic fatty liver disease.” The Turkish Journal of Gastroenterology: The Official Journal of Turkish Society of Gastroenterology, vol. 29, no. 2 (2018): 170-176
8. Fogacci F et al. “Effect of resveratrol on blood pressure: a systematic review and meta-analysis of randomized, controlled, clinical trials.” Critical Reviews in Food Science and Nutrition. Published online January 23, 2018.
9. Qin S et al. “Efficacy and safety of turmeric and curcumin in lowering blood lipid levels in patients with cardiovascular risk factors: a meta-analysis of randomized controlled trials.” Nutrition Journal, vol. 16, no. 1 (October 2017): 6
10. Deplanque X et al. “Proprietary tomato extract improves metabolic response to high-fat meal in healthy normal weight subjects.” Food & Nutrition Research. Published online October 4, 2016.