Dietary Supplements and Cardiovascular Health: Taming Triglycerides

While elevated cholesterol continues to hog the headlines as a presumed cause of heart disease, triglycerides are also increasingly being recognized as a potential troublemaker.

Like cholesterol, triglycerides are essential for life. Baldur Hjaltason, strategic business development and sales manager for EPAX AS (Aalesund, Norway), says, “Triglycerides are the main component of fat in our diet. They provide fuel for muscles and play an important role in the production of metabolic energy for many ongoing functions in the body. Triglycerides are also raw material for a long series of biological compounds that regulate how our cells deal with the food we eat. Only hours after eating a meal, signals are sent to various cells preparing them to react to what and how much we have eaten.”

Nevertheless, says the EPAX executive, as is true in almost all cases, too much of a good thing is a bad thing.

And, at present, says Jerry Wisler, president and CEO of Omthera Pharmaceuticals (Bedminster, NJ), “The overall dyslipidemia population in the United States is believed to be in excess of 100 million, with over 27 million of those diagnosed with hypertriglyceridemia.”

Steve Holtby, president and CEO of Los Angeles, CA–based Soft Gel Technologies Inc., says testing for triglycerides requires only a simple blood test. He adds, “On a lab report, normal levels are considered less than 150 mg/dL. Borderline high is 150 to 199 mg/dL. Once you reach the range of 200 to 499 mg/dL, your numbers are considered high. More than 500 mg/dL is designated very high.”

Christina Ehrhardt, global research manager for La Grange, IL–based Cognis Nutrition & Health, says, “In recent years, increased triglyceride levels have emerged as a risk factor for coronary heart disease independent of other blood lipid disturbances.” Wisler adds, “Very high triglycerides are associated with an increased risk of pancreatitis.”

The American Heart Association (AHA), which maintains offices in Dallas, TX, is on board with these assessments, saying, “Increasing evidence supports triglyceride concentration as a risk factor for cardiovascular disease.” On its website www.heart.org, the organization notes a link between the growing incidence of hypertriglyceridemia and the rising prevalence of obesity throughout the nation.

While most practicing doctors believe that statin drugs are the answer to corralling untamed triglycerides along with overall cholesterol, many in the natural products community-professionals and consumers alike-are unwilling to accept this one-size-fits-all solution.

Objecting to such side effects as muscle weakness, muscle breakdown, and CoQ10 depletion-all of which have been associated with the pharmaceutical products-enterprising suppliers and supplement manufacturers have researched and promoted a variety of natural alternatives.

Among these, the most prominent by far are omega-3 fatty acids, most notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Supported by studies going back decades, these substances, often found in coldwater fish, have even won virtually unanimous approval from the medical establishment itself.

Since 2006, AHA guidelines have urged “that people without documented coronary heart disease (CHD) eat a variety of fish, preferably oily fish (salmon, tuna, mackerel, herring, and trout), at least twice a week. People with documented CHD are advised to consume about one gram of EPA and DHA per day, preferably from oily fish, although EPA+DHA supplements could be considered in consultation with a physician. People who have elevated triglycerides may need two to four grams of EPA and DHA per day provided as capsules under a physician’s care.”

The supplement industry has met this perceived consumer need with scores, if not hundreds, of offerings. And health shoppers have responded by buying products by the proverbial bucketful. Diane Hnat, senior technical marketing manager for DSM Nutritional Products (Parsippany, NJ), cites Information Resources Inc. (IRI) data showing seven consecutive years of “double-digit monthly growth for the use of fish oil supplements.”

Omega Sea
ROPUFA 75EE, DSM’s trademark-protected entry into this market, is a concentrated fish oil in the form of an ethyl ester that Hnat says could provide the recommended amount of EPA and DHA in just three to six small fish oil capsules (#16 softgels) as opposed to approximately six to 12 typical fish oil caps (#20 softgels). Nonetheless, she warns, “To assume that triglyceride control [alone] will alleviate CVD risk would be shortsighted.” She cites the AHA’s 2006 revision of its Scientific Statement on Diet and Lifestyle, which emphasized the dangers of “the obesity epidemic” and identified a number of coronary disease risk markers, only one of which is triglyceride level. “Thus,” Hnat insists, “the approach must be multifactorial.”

Omthera also offers an ingredient that may be of value in controlling triglycerides. A recent press release announced that the company has reached agreement with FDA on a Special Protocol Assessment for the design of its planned Phase III registration clinical trial of Epanova, the firm’s patent-protected pharmaceutical compound for the treatment of patients with very high triglycerides. The release described Epanova as a “novel, ultrapure mixture of the free fatty acid forms of EPA and DHA.” The company said that its data point to an “improved and more predictable bioavailability as compared to the ethyl ester form found in prescription omega-3 products currently available.”

According to the release, “Triglyceride lowering with Epanova was previously observed in two large, placebo-controlled, randomized, double-blind, Phase III studies involving 748 Crohn’s disease patients with normal triglyceride levels for greater than or equal to 52 weeks, approximately 400 [patients] of which were treated with Epanova for remission of disease.”

Holtby says Soft Gel Technologies’ leading omega-3 ingredient, EZ Mega 3, “contains fish oil concentrate that has a patented three-component antioxidant system, which has been carefully developed to give it superior oxidative stability. Due to proprietary and patented deodorization and stabilization technology, there is no fishy smell or taste.”

From EPAX comes EPAX 6000TG, a marine-based omega-3 concentrate containing 300 mg/g of EPA and 200 mg/g of DHA. According to Hjaltason, EPA prevents triglyceride synthesis in the liver and the subsequent loading of low-density lipoprotein (LDL) particles, thereby reducing the risk of developing dangerous, small, dense cholesterol particles. DHA, meanwhile, provides signals to the genes to help speed up the body’s ability to burn fat.

Not only do omega-3 fatty acids lower the total triglyceride content in the blood, but they also have been shown to change the ratio of LDL and HDL in a positive way, he adds.

While most marine omega-3s are sourced from fish, Oslo, Norway–based Aker BioMarine is using a different form of sea life-krill. Eric Anderson, the company’s U.S. vice president of sales and marketing, who recently established an office in Metuchen, NJ, says that krill, defined as planktonic crustaceans and larvae, are lower on the food chain than fish (in fact, they are eaten by fish) and therefore are less likely to be contaminated with mercury, PCBs, and dioxins.

Branded as Superba Krill Oil, the firm’s product is said to provide the majority of its omega-3 fatty acids in the form of phospholipids rather than triglycerides or ethyl esters. As a result, says Anderson, citing a study performed in cooperation with researchers at Akershus University College and University of Oslo, Norway, “a lower dose of EPA and DHA is required when taking krill oil phospholipids.” The study, he reports, shows a reduction of plasma triglycerides in those subjects in the krill oil group having the highest baseline values. In addition to high bio-efficiency, he claims the following as advantages of krill over fish: no burping and no fishy odor or aftertaste.

Likewise, krill supplier Enzymotec (Israel) notes a link between triglyceride lowering and krill oil omega-3 fatty acids. The company says that a three-month, multicenter, randomized, 120–human subject clinical trial published in Alternative Medical Review found that Neptune-brand krill oil by Neptune Technologies & Bioresources (Québec) was effective in reducing triglyceride levels compared to both fish oil and placebo.

Additionally, the company adds, preclinical trials conducted in hyperlipidemic rats, obese rats, and high-fat-diet mice showed similar results in modulating triglycerides. The company says that while the exact mechanisms of this effect still need exploring, most likely they are related to the activity of EPA and DHA.

Omega Land
As already noted, not all omega-3 fatty acids come from the sea. This past summer, Cargill Health and Nutrition (Minneapolis) introduced Clear Valley Omega-3 Oil, a canola/flaxseed oil blend that meets the needs of consumers who prefer a vegetarian option. The company says the patent-pending ingredient enables food manufacturers to make a “good source of ALA (alpha linolenic acid) omega-3” or “excellent source of ALA omega-3” nutrient content claim on the front of the package. The new oil contains up to 30% ALA omega-3 and provides a minimum of 160 mg of ALA in most applications.

Among the reasons Willie Loh, PhD, vice president of Cargill’s oils and shortenings business, thinks food makers will be drawn to the new ingredient is that, “unlike fish oils, it is taste-neutral and won’t interfere with established flavor profiles. In addition, it is shelf stable for more than nine months, making it ideal for cookies, cereal bars, crackers, snacks, and spreads. Consequently, there’s no need for our customers to modify their recipes or formulas; they can simply replace their existing oil with Clear Valley Omega-3 Oil.”

Omega-3: Not the End, After All
Cholesstrinol is the principal omega-3 entry from Chicago, IL–based Source One Global Partners. Jesse Lopez, CEO and founder, describes the line as a “family of heart-healthy formulations” that recently received the United States Heart-Health Supplements Product Innovation of the Year Award from Frost and Sullivan, an internationally recognized research and consulting firm.

Lopez cites a peer-reviewed published study with 120 subjects showing a 34% reduction in triglyceride levels in just four weeks. The study period was 12 weeks, and the two ingredients tested were TocoSource palm tocotrienols and PMF-Source citrus polymethoxylated flavones, both supplied by Source One.

According to Lopez, “These are the two key ingredients we’ve formulated into Cholesstrinol HP; Cholesstrinol O3, which is our Omega Choice concentrated triglyceride EPA/DHA omega-3 with TocoSource palm tocotrienols and PMF-Source citrus polymethoxylated flavones; and our Cholesstrinol PS, where we feature SterolSource plant sterols. A daily dose of Cholesstrinol PS delivers 2400 mg of plant sterols.”

As the Source One example above points out, raw material and ingredient suppliers are looking not just at omega-3s, but at other substances, too, when it comes to control of triglycerides. Among these are the aforementioned tocotrienols and plant sterols, as well as gugulipids and green tea extract.

Sytrinol, an ingredient by Proprietary Nutritionals Inc. and distributed by Soft Gel Technologies, is a patented formulation consisting of palm fruit and citrus extracts that contain polymethoxylated flavones and tocotrienols. According to Soft Gel’s Holtby, the ingredient has been shown in several clinical trials to lower total cholesterol by 20%, LDL cholesterol by 22%, and triglycerides by 28%.

The Soft Gel executive says the PMFs modulate lipoprotein and lipid metabolism directly in the liver by decreasing apoprotein B needed for endogenous synthesis of LDL cholesterol, and inducing the suppression of diacylglycerol acyltransferase, an enzyme required for triglycerides synthesis.

Holtby also cites a 2002 research study published in Atherosclerosis. Ninety hypercholesterolemic human subjects were initially placed on the American Heart Association Step-1 diet and then were administered 25, 50, 100, and 200 mg/day of a tocotrienol-rich fraction (TRF25) of rice bran. The 100 mg/day dosage produced the maximum decreases in serum total cholesterol (20%), LDL cholesterol (25%), and triglycerides (12%).

Plant sterols, especially when combined with endurance training, is another natural lifestyle intervention that has been shown to decrease triglyceride concentrations along with total cholesterol and LDL cholesterol, while simultaneously increasing HDL cholesterol.

The authors of a report published in the April 2006 issue of The Journal of Nutritional Biochemistry concluded that plant sterols decrease both total and LDL cholesterol levels by reducing exogenous cholesterol absorption by way of cholesterol displacement in the intestinal lumen. Additionally, the intestinal membrane transport proteins, ABCG5, ABCG8, as well as NPC1L1, have also been implicated in plant sterol–mediated cholesterol lowering. Conversely, exercise decreases triglyceride levels by reducing hepatic very-low-density lipoprotein secretion and increasing skeletal lipoprotein lipase activity. In addition, endurance training was shown to increase HDL cholesterol levels by way of HDL subfraction alterations, in conjunction with changing reverse-cholesterol transport enzyme activities. Moreover, plant sterols and exercise may work synergistically to alter lipid levels by modulating lipoprotein transport, composition, release, and metabolism.

In another study, published in May 2010 by Molecular Nutrition & Food Research, consumption of plant sterols reduced plasma and hepatic triglycerides and modulated the expression of lipid regulatory genes and de novo lipogenesis in a certain class of laboratory mice.

Gugulipid, a trademarked extract of Commiphora mukul, is just one of several dozen ingredients offered by East Windsor, NJ–based Sabinsa Corp., a company that honors the ayurvedic tradition. Lakshmi Prakash, PhD, the company’s vice president of innovation and business development, says that Gugulipid contains guggulsterones, which, she adds, have “significantly reduced markers of inflammation in clinical studies.” Low-grade inflammation, she points out, is reported to result in high triglycerides.

Prakash lists the following as other Sabinsa offerings that have shown potential to reduce elevated triglycerides: alpha-lipoic acid; policosanol; Silbinol (Pterocarpus marsupium extract); Resvenox (resveratrol); Momordicin (Momordica charantia, or bitter melon extract); Salaretin (Salacia reticulata extract); Fenufibers and Fenusterols (fenugreek seed extracts); Tulsi (Ocimum sanctum extract); and Saberry (Emblica officinalis extract, or amla).

Green tea also has been proposed as a promising agent for triglyceride management. According to Dr. William Davis, whose blog runs at www.healthcentral.com, “The catechins (flavonoids) in green tea can reduce triglycerides by 20%. Approximately 600 to 700 mg of green tea catechins are required for this effect, the equivalent of six to 12 servings of brewed tea. (Tea varies widely in catechin content.) Nutritional supplements are also available that provide green tea catechins at this dose. The weight loss–accelerating effect of green tea may add to its triglyceride-reducing power.”

Indena S.p.A., which is headquartered in Milan, Italy, and has U.S. offices in Seattle, WA, offers Greenselect, a trademarked, caffeine-free extract from green tea leaves. Christian Artaria, marketing director and head of functional food development, says the ingredient is characterized by a high content (not less than 60%) of polyphenols. The main constituent is (-)-epigallocatechin 3-O-gallate, accounting for not less than 40% of the extract.

Artaria says that such other Indena products as Leucoselect Phytosome Grape Seed Extract and Oleaselect Olive Fruit Extract also can be utilized to help reduce and/or control triglycerides. He emphasizes that the health benefits of extra-virgin olive oil are well known as a key part of the vaunted Mediterranean-style diet, with FDA recommending daily consumption of 23 g of olive oil.

So where do triglycerides rank on the ever-growing list of heart-disease markers? Are they more important than cholesterol, HDL: LDL ratio, C-reactive protein, homocysteine, high blood pressure, diabetes, metabolic syndrome, the apple-shaped body, and/or many other conditions? Perhaps not, says Davis, but they “certainly should never be ignored.”

Sidebar:

Hibiscus for Heart Health

By Jennifer Kwok, Editor

Could anthocyanin-rich hibiscus extract (Hibiscus sabdariffa) be the next ingredient to watch for cardiovascular health? A study profiled recently by Marissa Oppel-Sutter, MS, in the American Botanical Council’s (ABC; Austin, TX) HerbalGram newsletter found that hibiscus extract may reduce blood glucose and triglyceride levels, as well as increase HDL cholesterol, in people with metabolic syndrome.

Published in the June 1, 2010, issue of Phytomedicine, the study analyzed the results of 51 metabolic syndrome subjects and 73 healthy control subjects who were divided into three treatment groups: dietary changes only, a powdered hibiscus extract only, and hibiscus extract plus dietary changes, for 31 days. Those assigned to the hibiscus extract took one capsule (100 mg) daily before breakfast.

Metabolic syndrome subjects who supplemented with hibiscus extract and made dietary changes experienced significant decreases in triglyceride levels, while control subjects who supplemented with hibiscus extract saw triglyceride levels decline as well. With hibiscus extract supplementation, both groups also saw improved ratios of triglycerides to HDL cholesterol levels.

“The hypolipidemic effect of hibiscus extract has been attributed to the presence of anthocyanins,” wrote Oppel-Sutter. “The authors write that more research is needed to define the chemical profile of hibiscus extract and to determine the active constituent(s). The results of this study are in agreement with prior clinical trials indicating the cardiovascular benefits of hibiscus, including hypotensive and hypocholesterolemic effects. The authors conclude that hibiscus extract is a useful complementary therapy for patients with metabolic syndrome.”

*Note: As part of ABC’s Adopt-an-Herb program, RFI Ingredients (Blauvelt, NY) has “adopted” hibiscus. For the next three years, the company will financially support the addition of scientific research on hibiscus to ABC’s HerbMedPro database.

Sidebar:

Doctors Say “Do” to Omega-3

By Jennifer Kwok, Editor

While opinions may vary in the medical community when it comes to dietary supplements, one most physicians agree on for overall heart health-including lowering triglycerides-is omega-3 fatty acids.

“There’s only one nonprescription treatment I recommend to lower triglycerides, and that’s omega-3 fatty acids,” says Michael F. Richman, MD, FACS, FCCP, (no relation to Alan Richman, the author of our main article). Richman is a board-certified cardiothoracic surgeon, the cholesterol medical expert on WebMD, and medical director for the Los Angeles–based Center for Cholesterol Management.

He recommends a high dose of omega-3 (approximately 4000 mg/day) for patients with high triglycerides. In a paper he wrote recently on the subject, he stated: “Early studies demonstrated that the major effect of omega-3 fatty acids on the lipid profile is to lower triglyceride levels between 10 to 45%, depending on the severity of the triglyceride level and the dose of omega-3 fatty acids used.”

“There’s clear and convincing data from epidemiologic and randomized controlled trials that show fish oil lowers the incidence of death in people who have had heart attacks or congestive heart failure,” he adds. “That’s solid data.”

American Heart Association (AHA) spokesperson Rachel K. Johnson, PhD, says AHA also stands behind omega-3. “At this point, I think the only supplements that can be recommended are omega-3 polyunsaturated fatty acids, in the form of DHA and EPA, for people with high triglycerides who are under a physician’s care.” However, she adds, the medical community has yet to reach consensus on an optimal dose or an optimal target population and cautions consumers to always consult a physician before taking supplements.

Both Richman and Johnson also highly recommend therapeutic lifestyle changes-stopping smoking, as well as exercising and losing weight-as effective ways to target triglycerides. Both point consumers toward an overall heart-healthy diet. “We’re focusing on an emphasis of healthy fats-mono- and polyunsaturated fats-as well as the quality of carbohydrate intake, focusing on whole grains as opposed to processed grains,” says Johnson. She adds that AHA is now also looking at scientific evidence that reducing added sugars can lower triglycerides.