Coloring Consumers Health with Carotenoids

Coloring Consumers Health with Carotenoids
As consumers seek functional foods with added value, suppliers are developing novel ways to help incorporate carotenoids into these products

by Heather Granato

Skittles candies invite consumers to Taste the Rainbow. Unfortunately, that rainbow is full of artificial flavors and colors, as well as sugar. Instead, functional food manufacturers are helping deliver a rainbow of functional nutrients that promote good health.

One of the most varied and functional classes of pigments in nature is the carotenoids. These natural, fat-soluble pigments occur in plants, bacteria, fungi and animals, putting the red in tomatoes, yellow in autumn leaves and pink in flamingos.

These pigments also offer a range of health benefits, which consumers are seeking through both dietary supplements and functional foods. Companies are recognizing carotenoids are not only pigments in foods and beverages, but provide significant health benefits and business advantages, said Larry Line, vice president, international, for Eustis, Fla.-based U.S. Nutra, the supplier of Zanthin natural astaxanthin. Functional foods with positive health benefits tend to be more profitable and differentiate ones product from another.

Science and technology have come a long way from the early 1830s, when a scientist isolated the first carotenoid from carrots. Today, there are more than 700 known natural carotenoids; as many as 50 may be absorbed and metabolized by the human body. To date, however, only 14 have been identified in human serum.

Carotenoids have a distinctive pattern of alternating single and double bonds in a polyene backbone. The chain may be terminated by cyclic endgroups (rings) and may be complemented with oxygen-containing functional groups. The hydrocarbon carotenoids are known as carotenes, and those with oxygenated derivatives of these hydrocarbons are xanthophylls.

In plants and animals, carotenoids act as antioxidants. They can quench singlet oxygen and scavenge free radicals to prevent or terminate oxidative chain reactions. Carotenoids are absorbed in the intestine with dietary fat and are stored primarily in the lipid portions of the body. Approximately 80 percent of carotenoids are distributed in adipose tissues, with smaller amounts found in the liver, muscle, adrenal glands and reproductive organs.

In humans, dietary carotenoids are thought to provide a range of health benefits, according to researchers from the U.S. Department of Agriculture (USDA) Human Nutrition Research Center on Aging at Tufts University in Boston.1 They noted beta-carotene, lycopene, lutein and zeaxanthin have been the most studied carotenoids. Their activity in singlet oxygen quenching is variable, with lycopene and beta-carotene being the most active.2

Health Effects

General and specific studies have underscored the importance of carotenoids in the human diet. The protective effects of carotenoids against serious disorders such as heart disease, cancer and eye diseases have been demonstrated in various animal and human studies, said Yousry Naguib, Ph.D., manager of new product development with Soft Gel Technologies in Los Angeles. Some carotenoids can also improve immune function by stimulating lymphocytes and natural killer (NK) cells.

This ability to stimulate overall health is one reason the National Cancer Institute (NCI) cosponsored the national 5 a Day for Better Health Program, which encourages Americans to eat five to nine servings of fruits and vegetables every day to reduce the risk of cancer and other diseases. The array of phytonutrients has been studied for its impact on cancer prevention. Beta-carotene, alpha-carotene, lutein, zeaxanthin, lycopene, cryptoxanthin, astaxanthin and more may all reduce oxidative damage that can be hazardous to cellular health.3

Studies on produce and mixed carotenoids underscore the importance of consuming a range of these beneficial nutrients. All the carotenes should be present at significant levels to work synergistically and confer health benefits associated with mixed carotenoids, said W.H. Leong, vice president of Edison, N.J.-based Carotech, the supplier of Caromin mixed carotene complex from palm fruit.

In the specific area of cancer prevention, it has been suggested carotenoids work by stimulating immune function and inhibiting lipid peroxidation in tumors. A study conducted at Washington State University in Pullman examined the impact of plasma carotenoid concentration on mammary tumor volume in mice.4 The researchers found beta-carotene, canthaxanthin and astaxanthin inhibited tumor growth and peroxidation activity in the tumors. Another study found palm carotene (as Caromin) supplementation modulated the immune system by increasing peripheral blood NK cells and suppressing the growth of MCF-7 human breast cells.5

Because carotenoids are stored in the reproductive organs, cancers affecting the breast and prostate have been areas of particular research focus. One case-controlled study from the New York University School of Medicine reviewed blood concentrations of carotenoids in 540 women over 10 years.6 The researchers found an increased risk of breast cancer in women with lower levels of beta-carotene, lutein, alpha-carotene and cryptoxanthin. In fact, the risk of breast cancer approximately doubled among women with the lowest levels of beta-carotene compared to those with the highest levels. A similar study in Maryland found median concentrations of carotenoids were significantly lower in women with breast cancer than those without.7

As in breast cancer research, many population studies have shown a reduced risk of prostate cancer with higher plasma carotenoid levels. Researchers from the University of California, Los Angeles, investigated the effects of carotenoids on the risk of prostate cancer.8 Comparing 65 patients with prostate cancer to 132 cancer-free controls, they found an inverse association between lycopene, zeaxanthin, lutein and cryptoxanthin levels and prostate cancer incidence. Lycopene specifically has been found to suppress the growth and dissemination of neoplastic prostate cells,9 though some evidence has not shown an association between lycopene and prostate cancer.10

Both synthetic and natural source lycopene ingredients are available in the nutraceutical industry. Two of the primary suppliers of synthetic lycopene are BASF and DSM Nutritional Products. BASF received notice from the Food and Drug Administration (FDA) in May 2003 with no questions on the companys self-affirmation of its crystalline lycopene as GRAS (generally recognized as safe). Among the categories BASF affirmed as GRAS were breakfast cereals, drinks, instant soup and nutrition bars, at levels ranging from 0.5 percent to 7.0 percent. In its FDA letter, BASF noted it might submit a color additive petition for its synthetic lycopene, but that use is not yet approved. DSM lycopene is also affirmed GRAS. DSM and BASF both offer fat- and water-dispersible products for food and beverage applications.

The primary supplier of natural-source lycopene is LycoRed Industries, producers of Lyc-O-Mato natural lycopene complex. The company contracts with farmers to grow its non-genetically modified, high-lycopene tomatoes and processes the fruit on site at its Israel plant. We control the process from seeds to processed goods, said Diane Fremont, LycoReds sales director. Fremont noted the company has self affirmed Lyc-O-Mato as GRAS and has an application pending for FDA approval as a natural colorant.

Beyond cancer prevention, lycopene also plays a role in mediating cardiovascular disease (CVD). Researchers in Finland concluded men with low plasma levels of lycopene had an 18-percent increase of intima-media thickness (IMT) of the carotid artery wall versus those with higher levels.11 Further work from the same research group found serum lycopene concentration may play a role in the early stages of atherosclerosis.12

Other carotenoids also play a role in prevention of CVD, possibly by protecting blood lipids against oxidation. In vivo and in vitro work by French researchers showed carotenoids can transfer between lipoproteins preferentially.13 Beta-carotene and astaxanthin were found to inhibit peroxidation of lipids,14 and lutein protected against atherosclerotic development in mice models.15 Also, astaxanthin has been shown in a study at the National Institute of Health and Nutrition in Tokyo to significantly inhibit LDL (low-density lipoprotein) oxidation in 24 volunteers.16

Astaxanthin is an extremely powerful antioxidant, said Kelly Moorhead, technical sales with Kailua-Kona, Hawaii-based Cyanotech Corp., the supplier of BioAstin natural astaxanthin. The structure of natural astaxanthin allows it to cross cell membranes, showing activity in both lipid and aqueous portions of the cell.

The third primary focus of carotenoid research is in the field of eye health. The eyes are subject to a great deal of UV radiation and related oxidative stress, but are loaded with high levels of fat-soluble carotenoids to both absorb blue light (thereby protecting the photoreceptor cell layer) and scavenge singlet oxygen. In particular, high levels of lutein are found throughout the retina, with concentrated levels of zeaxanthin located in the macular region.

Supplemental lutein and zeaxanthin increase macular pigment density, filtering greater amounts of short-wave light and reducing the effects of oxidative damage.17 There is a great deal of evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration (AMD), an irreversible process that is a major cause of blindness in the elderly.18 In addition, researchers from Universitair Medisch Centrum Utrecht in The Netherlands found an inverse relationship between macular pigment density and lens optical density, indicating lutein and zeaxanthin may retard aging of the lens and cataract development.19

There are two primary delivery methods for lutein. It can be supplied as purified lutein, in which the lutein is isolated and purified from the source material, or as lutein esters, in which the lutein is still bound with the plant fats.

Kemin Foods in Des Moines, Iowa, holds a number of U.S. patents on the use of purified lutein; it supplies the ingredient as FloraGLO Lutein. Kemin has affirmed FloraGLO as GRAS for a wide range of categoriescommon applications include nutritional beverages, vegetable juices and cereals with inclusion levels between 0.3 mg to 3.0 mg of lutein per serving. Kemin has developed multiple delivery forms to address the diverse formulation needs when including FloraGLO Lutein in a variety of consumer products, said Amy Cone, director of marketing for Kemin.

Other suppliers promote lutein esters as a more natural form; suppliers include Fairfield, N.J.-based Buckton Scott Nutrition (OptiCare lutein esters) and Cognis Nutrition & Health (Xangold lutein esters) in La Grange, Ill., which holds GRAS status for Xangold in several food applications. Both ingredients are available in beadlet forms, with water-soluble forms close to launch.

Astaxanthin also has application in eye health. U.S. Patent No. 5,527,533, assigned to U.S. Nutra, involves the use of astaxanthin to protect from ocular and neurodegenerative diseases. The companys Zanthin ingredient is available in oleoresin, compressible beadlet and cold-water dispersible beadlet forms.

Formulation Issues

Demand for carotenoids for use in food and beverage products is growing at a high rate, according to most suppliers. Interest from food companies is not increasingits booming, said David Eckert, Cognis business director for North America.

Barry Kaufman, BASFs senior product manager, agreed with the assessment. We are seeing carotenoids in such products as cereals, nutrition bars and functional beverages, he said. You name an area of nutrition, and companies are trying to fortify it with carotenoids.

Juices are one of the most common product categories incorporating carotenoids. Hain Pure Foods, for example, introduced two new beverage products this summer incorporating FloraGLO Lutein. However, the range of products incorporating carotenoids is expanding exponentially with competing companies jockeying for position. We are receiving a considerable number of inquiries from a variety of brands in existing food categories where FloraGLO Lutein is used, and in other product categories in the food and personal care industries, Cone said.

While including carotenoids in a new product can offer differentiation on a crowded store shelf, these ingredients need consideration in product development. Formulating with carotenoids or antioxidants is a new thing to many food companies, Eckert said. So customers are looking for expertise to address the challenges resulting from the sensitive nature of carotenoids to oxidation. Other factors to consider include how adding carotenoids will impact color, flavor and mouth feel depending on the amount and form used.

First, formulators must consider carotenoids lipophilic nature. Carotenoids are not water soluble and only slightly oil soluble, said Karen Todd, DSMs senior marketing manager for new ingredients and business development. To overcome the issue, many suppliers are offering water-dispersible beadlets, which are particularly useful in beverage fortification. One trick to avoid beverage ringing is to first make a carotenoid stock solutiona pre-dilution of the beadlets in waterprior to adding it into the beverage production line, Todd said.

In addition to posing special formulation requirements, carotenoids also need special handling to avoid oxidation. Carotenoids are highly volatile and unstable by nature, an attribute that makes them such great antioxidants, Todd said. At the same time, it is critical to develop highly stable and user-friendly formulations for use in a variety of applications.

Line agreed with the assessment, adding the efficacy of a stable product is often tied to the cost of achieving that stability. He added the challenges of bioavailability and solubility also must be addressed in formulation. There are significant differences in the bioavailability of different carotenoids, even natural forms that may have different chirality, Line said. Ideally, bioavailability is enhanced with solubility and, in the case of lipid-soluble carotenoids, some oil or lipids in the meal or dose form enhance biological absorption.

Manufacturers must also decide between natural and synthetic carotenoid ingredients. Among the factors to consider are the application, bioavailability, research support (particularly if making label claims) and cost.

Most of the current research in beta-carotene, for example, is on synthetic beta-carotene, including the 20-year Physicians Health Survey conducted by Harvard, Kaufman said. BASF has supported this study of more than 15,000 physicians for the 20 years of its duration, and results are expected in the next few years.

There is ongoing discussion regarding whether the body assimilates natural and synthetic carotenoids differently, or if they have different effects on health. The human body does not differentiate between synthetic carotenoids and the carotenoids found in foods, Todd said. For example, DSM lycopene has a similar trans-cis isomeric profile compared to lycopene found in processed tomato products.

However, Line said there could be major differences in bioavailability between natural and synthetic carotenoids. Small differences in the stereochemistry or chirality can and do have huge effects on biological activity, he said. Nature is incredibly selective in the forms of carotenoids an organism can use effectively.

Finally, manufacturers must examine the question of whether to use single carotenoids or a mixture. Even suppliers of single carotenoid ingredients consider it important to ensure high intake of all the carotenoids. Formulators should consider the value of a cocktail of different carotenoids, Moorhead said. Also, they should consider using products such as astaxanthin to provide a high degree of antioxidant activity at very low concentrations.

Whatever the application, suppliers are working to extend GRAS status and develop new technologies to capitalize on growing consumer interest in the carotenoids. Consumer interests and influential health and nutrition opinion leaders are generating a growing health consciousness in the broad consumer marketplace, Cone said. Food companies interested in or committed to functional or fortified foods that can impact specific human health conditions are wise to seriously explore these possibilities.

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