Power of Pigment

Carotenoids fight free radicals to protect eye and heart health and fend off cancer

The Antioxidant Powers of Bilberry and Grape Seed Extract · Story References

Picture of lutein soft gels courtesy of Kemin Fodds.

Carotenoids are a group of naturally occurring fat-soluble pigments found in plants that are commonly recognized for their antioxidant properties. More often than not, carotenoids are studied in groups rather than individually, perhaps due to their synergistic effects in the body. "The interesting thing about carotenoids is that they're tissue-specific, meaning each one has an affinity for specific body tissues," said Sara Lovelady, marketing director for Santa Cruz, Calif.-based Rainbow Light. "Lycopene, for example, accumulates in the breasts, lungs and reproductive organs. Zeaxanthin, on the other hand, is selectively accumulated in the macular region of the retina of the eye. So if you only take one carotenoid, you get very limited protection."

Some of the more common groupings include alpha-carotene, beta-carotene and beta-cryptoxanthin, which are precursors to vitamin A, as well as lutein and zeaxanthin, which are commonly studied for eye health because of their concentrated presence in the macula. "Recent evidence introduces the possibility that lutein and zeaxanthin may protect against the development of the two common eye diseases of aging: cataract and macular degeneration," according to researchers from the University of Wisconsin, Madison. "This potential and the lack of other effective means to slow the progression of macular degeneration have fueled high public interest in the health benefits of lutein and zeaxanthin, and the proliferation of supplements containing them on pharmacy shelves."¹

And the public interest seems to be expanding from the most well-known carotenoids to the category as a whole. "Carotenoids have received a lot of positive attention due to the emerging research over the past 10 years that supports their role in disease prevention, such as lutein preventing macular degeneration, the leading cause of blindness in adults over 65," Lovelady said. "Lycopene is now a household term, and people know it helps prevent prostate cancer. I think the consumer audience hit critical mass once Dr. Andrew Weil recommended that people start taking carotenoids daily."

With more than 500 known carotenoids existing in nature, there are relatively few that are commonly included in clinical trials and retrospective research. The following list highlights some of the more prevalent carotenoids in recent research, although many of the studies mentioned here include more than one carotenoid.

Alpha-carotene

Alpha-carotene is one of three carotenoids that can be converted to vitamin A in the body; two others are beta-carotene and beta-cryptoxanthin. The vitamin A activity of these compounds in foods is measured as retinol activity equivalents (RAE), according to the National Academy of Sciences (NAS), with 1 RAE being equal to 24 mcg of alpha-carotene and 1 mcg of vitamin A.

Alpha-carotene has been indicated in recent research for reducing the risk of cataracts. One trial out of the University of Southampton in England noted that of 372 subjects, those with the highest plasma concentrations of alpha-carotene, as well as beta-carotene, exhibited the lowest risk for nuclear cataract.²

Researchers from the Harvard School of Public Health linked alpha-carotene intake to a reduced risk of lung cancer. In a large study population of 46,924 men and 77,283 women, alpha-carotene intake, as well as intake of lycopene, were associated with a significant reduction in the risk for lung cancer. Specifically, in subjects who never smoked, those in the top quintile of alpha-carotene intake exhibited a 63-percent lower incidence of lung cancer compared to those in the bottom quintile of alpha-carotene intake.³

Astaxanthin

Astaxanthin is a carotenoid derived from algae and is indicated in numerous health conditions, ranging from performance nutrition to immune health.

According to a white paper published online by La Haye Laboratories Inc. in Redmond, Wash., astaxanthin supplementation increased strength and endurance in healthy young male subjects compared to placebo.

Astaxanthin may also be able to improve performance in people with rheumatoid arthritis, according to unpublished research conducted by Kailua-Kona, Hawaii-based Cyanotech Corp. The double blind, placebo-controlled study was conducted by the Health Research and Studies Center in Los Altos, Calif., and results will be presented in San Antonio, Texas, at the American College of Nutrition scientific meeting in October.

Earlier this year, Cyanotech received a notice of allowance from the U.S. Patent and Trademark Office stating it would issue the company a patent covering the use of natural and synthetic astaxanthin, in both oral and topical applications, as a single active ingredient to retard and prevent sunburn. Cyanotech also has a use patent for astaxanthin in correlation with reducing the severity and pain associated with carpal tunnel syndrome.

Astaxanthin is a potent anti-inflammatory, according to a 2001 research review published online by La Haye Laboratories. Because of its anti-inflammatory properties, it may be effective for managing acute and chronic inflammation caused by diseases such as arthritis, eczema and psoriasis.

Astaxanthin has been studied for its role in cancer prevention. When compared to beta-carotene and canthaxanthin for slowing or stopping tumor growth, astaxanthin was shown to dose-dependently reduce mammary tumor growth. Astaxanthin also reduced tumor growth more effectively than the other two carotenoids, although all three demonstrated a positive effect against tumor volume.⁴ Astaxanthin exerts anti-tumor activity through enhancing immune responses, according to researchers at the University of Minnesota in Minneapolis.⁵

Beta-carotene

Beta-carotene, sometimes called provitamin A, is the most abundant precursor of vitamin A. Found in fruits and vegetables, beta-carotene consists of two linked molecules of vitamin A.

When taken in combination with simvastatin (a cholesterol-lowering drug), niacin and other antioxidants (vitamin C, vitamin E and selenium), beta-carotene was found to reduce plasma cholesterol, triglycerides and low-density lipoprotein (LDL or "bad") cholesterol. However, simvastatin plus niacin was more effective without the antioxidants for increasing levels of high-density lipoprotein (HDL or "good") cholesterol.⁶

In terms of eye health, beta-carotene was linked with a reduced risk of cataracts in the Roche European American Cataract Trial (REACT). Of 158 patients who were followed for three years, those taking beta-carotene--in addition to vitamins C and E--had a slower rate of cataract progression.⁷

Studies have also linked beta-carotene to a reduced risk of breast cancer. One trial involving more than 500 subjects indicated women in the highest quintile of beta-carotene intake had half the risk of developing breast cancer as those women in the lowest quintile.⁸

In terms of lung cancer, however, beta-carotene has been controversial. Some studies show the nutrient has benefits while others show none, according to a research review of three beta-carotene intervention trials. The same research review indicated beta-carotene intake may actually increase the risk of lung cancer among smokers.⁹

Beta-cryptoxanthin

Similar to alpha-carotene and beta-carotene, beta-cryptoxanthin is a precursor of vitamin A.

Beta-cryptoxanthin may have application in the realm of cancer prevention. Researchers from the University of Southern California in Norris reviewed data from 18,244 men in Shanghai, China, and discovered men with the highest serum levels of beta-cryptoxanthin had a significantly lower risk of developing lung cancer.¹⁰ The researchers looked at other carotenoids as well--alpha-carotene, beta-carotene, lycopene, lutein and zeaxanthin--but after smoking status was taken into account, these carotenoids did not seem to affect the risk of lung cancer development.

Researchers from Maastricht University in The Netherlands discovered, after analyzing data from 120,852 subjects, that beta-cryptoxanthin intake was inversely related to the incidence of bladder cancer. Researchers concluded that of the nutrients studied--alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin and lycopene--only beta-cryptoxanthin was inversely associated with the risk of bladder cancer.¹¹

Canthaxanthin

Canthaxanthin is present in numerous fruits and vegetables, as well as some red- and pink-hued animals, such as salmon. Canthaxanthin is used as a food and drug colorant and has been indicated for cancer prevention and skin protection.

In terms of cancer prevention, the research on canthaxanthin does not seem to show a benefit, although it does not show a detriment either. Researchers from the Hokkaido University in Japan investigated the effects of various carotenoids on reducing cancer cell growth in vitro, but they concluded canthaxanthin did not affect the growth of prostate cancer cells.¹² Nor did canthaxanthin stop the growth of human breast cancer cell lines, according to researchers from Tufts University in Boston.¹³

As for skin protection, canthaxanthin is recommended as an oral supplement by manufacturers, although the research proving its efficacy is dated. In a 1985 journal, researchers documented the efficacy of oral canthaxanthin, in combination with beta-carotene, for its photoprotective effects. The carotenoid mixture was found to be beneficial and protective in patients with pigmentation disorders.¹⁴

Lutein

While lutein occurs in numerous foods, the highest concentrations of lutein occur in marigolds, which are the source of most commercial lutein. Commercially sold lutein can be sold as lutein esters or purified lutein. Lutein is most commonly associated with eye health because it is one of the two carotenoids found in high concentrations in the macula.

It is suspected that lutein filters out potentially damaging forms of light, thereby protecting the macula from oxidative damage. By blocking light damage, lutein is thought to protect the eye against various conditions, including age-related macular degeneration and cataracts.¹⁵

The third National Health and Nutrition Examination Survey (NHANES) evaluated the relationship between dietary lutein and zeaxanthin, and the presence of age-related maculopathy. While researchers said there were no overall observations linking carotenoids to age-related maculopathy, they noted that higher dietary levels of lutein and zeaxanthin were associated with lower rates of pigmentary abnormalities, which are generally early signs of age-related maculopathy.¹⁶

Lutein's propensity for increasing macular pigment density is suspected to be one of its mechanisms of action in protecting eye health. Natural lutein esters have been shown to increase macular pigment density by 20 percent, as well as increase blood lutein levels.¹⁷

Perhaps because of the increasing scientific support for the use of lutein in eye health, many eye doctors promote lutein intake. According to a study conducted by Cedar Rapids, Iowa-based Jefferson Davis Associates and commissioned by Des Moines, Iowa-based Kemin Foods (manufacturer of FloraGlo® brand lutein), more than 90 percent of eye doctors (of 150 ophthalmologists and 150 optometrists surveyed) believe poor nutrition plays a role in the development of common eye diseases and lutein plays an important role in promoting eye health. The study also found that 84 percent of eye doctors currently recommend lutein to their patients and 80 percent of these eye doctors believe regular use of lutein is helpful in maintaining eye health.

Lutein may also be relevant in terms of cancer prevention. Researchers in Italy compared 1,031 cases of ovarian cancer with 2,411 control cases and discovered an inverse association between lutein/zeaxanthin intake and the incidence of ovarian cancer. Researchers noted this relationship may be due to a high intake of fruits and vegetables.¹⁸

Lutein is also thought to have a role in protecting heart health, according to animal research conducted at the University of Southern California in Los Angeles. Scientists demonstrated that lutein supplementation reduced the thickening of artery walls, thereby seeming to prevent atherosclerosis.¹⁹ Additional research has linked lutein intake to a reduced risk of stroke.²⁰

Lycopene

Lycopene is the substance that gives tomatoes and several other fruits their deep red color. Under normal conditions, the concentration of lycopene in human plasma is greater than beta-carotene and other dietary carotenoids.

Lycopene is commonly studied in the realm of cancer prevention, particularly prostate cancer. According to an analysis of the Health Professionals Follow-Up Study, dietary lycopene intake was associated with a reduced risk of prostate cancer. In particular, this association was noted after high intakes of tomato sauce, the primary source of bioavailable lycopene.²¹ And, supplemental lycopene (as as Lyc-O-Mato®, manufactured by LycoRed/Biodar) has also been shown to stop the growth of prostate cancer.²²

Lycopene has also been linked to a significantly reduced risk of ovarian cancer, especially among premenopausal women, according to researchers from Brigham and Women's Hospital in Boston. Researchers reported intake of lycopene from tomato sauce had a strong protective effect.²³

Lycopene has also been shown to reduce the risk of lung cancer. Harvard researchers reviewing the Health Professionals Follow-Up Study and the Nurses Health Study linked diets rich in tomato-based products to a reduced risk of lung cancer. The researchers noted that those consuming the highest dietary amounts of lycopene, in addition to mixed carotenoids (alpha-carotene, beta-carotene, lutein and beta-cryptoxanthin) had a 20-percent to 25-percent reduced risk of lung cancer.²⁴

In addition to cancer prevention, lycopene has been touted for its role in heart health. Studies have shown that lycopene intake--in the form of tomato juice, spaghetti sauce and tomato oleoresin--significantly decreased serum lipid peroxidation and LDL oxidation, which researchers noted may reduce the risk of coronary heart disease.²⁵

In terms of skin protection, lycopene has been reported to protect against ultraviolet light-induced erythema, an abnormal redness of the skin caused by capillary congestion. Subjects consuming tomato paste (which contains lycopene) and olive oil rather than olive oil alone for 10 weeks exhibited a 40-percent lower incidence of erythema.²⁶

While it has been suggested that lycopene may enhance immune function, recent findings failed to demonstrate this effect. Patients were split into one of three groups to receive either low doses of lycopene, beta-carotene or placebo for 12 weeks. At the end of the study period, researchers noted no enhancement of cell-mediated immunity in either of the carotenoid treatment groups.²⁷

Zeaxanthin

In addition to lutein, zeaxanthin is one of the two carotenoids that occurs in high concentrations in the retina of the eye. The greatest amounts of zeaxanthin occur in the macular region, whereas lutein is distributed throughout the entire retina. These compounds are closely related and often occur together in nature. For this reason, zeaxanthin and lutein are often discussed together.

Similar to lutein, zeaxanthin has two main functions: to absorb the potentially harmful blue-violet wavelengths of light energy that come into the eye and to fight free radical damage. Zeaxanthin absorbs the potentially toxic wavelengths of light, thereby protecting the eye from light-induced ultraviolet phototoxicity, which can cause free radical damage and may potentially lead to eye disease.²⁸

Individuals whose diets provide greater amounts of dietary zeaxanthin and lutein have a reduced incidence of cataracts, according to researchers from the Harvard School of Public Health. Men enrolled in the Health Professionals Follow-Up Study who were in the top quintile of zeaxanthin and lutein consumption had a 19-percent reduction in the risk of cataract compared to men in the lowest quintile of zeaxanthin and lutein consumption.²⁹ Another study examined five different antioxidants and demonstrated that only lutein/zeaxanthin were associated with a reduced risk of nuclear cataracts. Individuals in the top quintile of lutein/zeaxanthin consumption were 50 percent less likely to develop a cataract compared to individuals in the lowest quintile of consumption.³⁰

Similar to lutein, zeaxanthin may have a role in reducing the risk of age-related macular degeneration. Lower retinal levels of zeaxanthin and lutein were noted in cases of macular degeneration compared to controls. Individuals in the top quintile of zeaxanthin and lutein levels were found to have an 82-percent lower risk of developing age-related macular degeneration compared to individuals in the bottom quintile.³¹ Additional research noted that individuals with high consumptions of zeaxanthin and lutein had a 40-percent reduced risk of developing age-related macular degeneration.³²

Zeaxanthin may also be a factor in cancer prevention. Among a group of 98 patients with different gastrointestinal malignancies, the serum levels of zeaxanthin were significantly higher in the healthy subjects compared to cancer patients.³³

Zeaxanthin, lutein and other carotenoids are especially effective at quenching free radicals when used synergistically. Researchers at Rutgers University conducted an in vitro study to determine the synergistic antioxidant capabilities of a branded carotenoid combination. The mixture (as Zealutein®, by Sabinsa Corp.) contained zeaxanthin, lutein, capsorubin, capsanthin and a branded black pepper extract (as Bioperine®, by Sabinsa Corp.). This unpublished study demonstrated that the mixture had potent antioxidant activity and inhibited lipid peroxidation.

Carotenoids, as a group, are gaining popularity at the retail level. With lutein being added to various functional food items and lycopene from tomato sauce being touted for its bioavailability, carotenoids are very much in the public eye. However, consumers may still have questions. "Carotenoids are pretty technical, so education is key," Lovelady said. "I think the message needs to be total body antioxidant protection. ... Also, keep in mind who the audience is for carotenoid products--mainly aging adults or those in their 30s and 40s who are interested in preventive care. Any marketing programs should be tailored to that audience."

Editor's note: Some content for this story was provided by Intramedicine, found at www.intramedicine.com.

The Antioxidant Powers of Bilberry and Grape Seed Extract

In addition to carotenoids, flavonoids and proanthocyanidins are antioxidant compounds derived from various fruits. Bilberry, for example, contains a flavonoid complex of anthocyanosides, and grapeseed extract contains oligomeric procyanidins (OPCs)--both of which fight free radicals throughout the body and offer various health benefits.

Bilberry (Vaccinium myrtillus) is a free radical fighter and its active constituent is a flavonoid complex, including proanthocyanidins, that is said to enhance eye health. "Possible mechanisms of action for its effects on ophthalmic conditions include its ability to protect against the breakdown of rhodopsin (retinal purple), a light sensitive pigment located in the rods of the retina, and its ability to regenerate rhodopsin," according to Herbal Medicine: Expanded Commission E Monographs (Integrative Medicine Communications, 2000). "It may also provide vasoprotection by decreasing capillary fragility and permeability."

Bilberry is thought to benefit cataract patients due to its antioxidant activity and flavonoid content, which may also lend it to improving symptoms of glaucoma.³⁴ And, while bilberry has been suggested for improving night vision, recent research does not back up this use of the botanical.³⁵

Grape seed extract also contains proanthocyanidins and has been recommended in terms of eye health. Research conducted in the late 1980s indicated grape seed extract can improve night vision in healthy subjects. However, the more contemporary use of grape seed extract is for heart health.

Researchers from Creighton University in Omaha, Neb., compared the antioxidant powers of grape seed extract to those of vitamin C, vitamin E and beta-carotene. "These experiments demonstrated that [grape seed proanthocyanidin extract] is highly bioavailable and provides significantly greater protection against free radicals and free radical-induced lipid peroxidation and DNA damage than vitamins C, E and beta-carotene," the researchers wrote. They went on to add that grape seed extract induced cell death in various human cancer cell lines, and in animal models, it protected against liver and kidney damage induced by acetaminophen overdose and demonstrated heart-protective properties. And, topical application of grape seed proanthocyanidin extract was found to reduce sun damage in humans.³⁶

Based on the hypothesis that red wine consumption is beneficial to heart health, researchers from the University of Debrecen in Hungary conducted animal research to determine whether red grape seed proanthocyanidin intake could improve recovery after heart trauma. The researchers concluded that grape seed proanthocyanidins improved heart recovery because of their antioxidant properties.³⁷

While commonly noted for their presence in bilberry and grape seed extract, proanthocyanidins are also found in cranberries, black currants, and green and black tea.

Story References

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