September 2016 Issue

Antioxidants: The Carotenoid Color Wheel
By Densie Webb, PhD, RD
Today's Dietitian
Vol. 18 No. 9 P. 12

When you hear the word "carotene," what's the first thing that comes to mind? Beta-carotene? Maybe lycopene or lutein? The fact is, there are more than 600 naturally occurring carotenoids synthesized by plants, algae, and bacteria. However, only about 40 are present in the American diet, and fewer than that (20) are measurable in tissue and serum, a prerequisite to studying their health effects. Several population studies have found an association between consuming foods—mainly fruits and vegetables—rich in carotenoids and a reduced risk of several diseases, including cancer, macular degeneration, and cardiovascular disease.

Carotenoids are the compounds that imbue the bright yellows, brilliant oranges, and plush reds of many fruits and vegetables; think carrots, red peppers, blood oranges, pumpkin, squash, beets, and sweet potatoes. They're also present in dark green leafy vegetables like spinach and kale, but the carotenoid color is masked by the green of chlorophyll. In marine life, carotenoids are found in the pigments of algae, shrimp, salmon, and crab. Each of these foods is a different carotenoid capsule. These colorful compounds can be divided into two broad groups: carotenes (eg, α-carotene, β-carotene, lycopene) and xanthophylls (eg, β-cryptoxanthin, lutein, zeaxanthin). Many more fall within each group, but those discussed here are the carotenoids most commonly found in the American diet.

While several carotenoids are believed to possess disease-preventing properties, the only essential function recognized to date is as a source for vitamin A. Known as provitamin A carotenoids (α-carotene, β-carotene, and β-cryptoxanthin) they can be converted in the body to vitamin A.1 Beta-carotene in foods has 1/12 the vitamin A activity of retinol (preformed vitamin A). The vitamin A activities of α-carotene and β-cryptoxanthin have only 1/24 that of preformed vitamin A. So, while they're sources of vitamin A, they aren't as efficient providers of vitamin A as that found in milk, for example, which is present as preformed vitamin A.

While more research is needed in all areas related to carotenoid consumption and disease prevention, the following is what is known today.

Cancer
Lung and prostate cancers are the most studied cancers in association with carotenoid consumption or supplementation. Several promising studies have shown a protective effect of dietary β-carotene against lung cancer, but subsequent studies haven't found the same benefit. One long-term prospective study, which looked at the effects of β-carotene supplementation, found that supplementation increased the risk of developing lung cancer among current and former smokers. A Finnish study found a protective effect of dietary lycopene, serum β-carotene, β-cryptoxanthin, lutein, and zeaxanthin against lung cancer, but not dietary β-carotene.2 A systematic review of prospective studies concluded that if any protective effect exists from the consumption of dietary carotenoids, it's likely to be small.3 Research continues, and a recent study from South Korea found that high serum levels of α-carotene and β-cryptoxanthin were significantly associated with a lower risk of dying from lung cancer.4

As with lung cancer, several population studies have found an association between consumption of lycopene-rich foods, especially tomatoes and tomato products, and a reduced risk of prostate cancer. Lycopene also is found in watermelon, papaya, and red grapefruit. However, while a Cochrane review in 2011 and a meta-analysis in 2015 cited positive findings, both studies concluded that there wasn't enough evidence to either support or deny a benefit of lycopene against prostate cancer.5,6 Earlier, in 2007, the American Institute for Cancer Research in Washington, D.C., concluded in its review of the literature that lycopene is probably protective against prostate cancer. For those studies that found a positive effect, the benefit appeared to be dose dependent, and there was a blood level threshold (>85 μg/dL) after which the benefit no longer increased. It also has been suggested that lycopene supplementation might reduce the negative effects of radiation therapy for cancer.7

An analysis of eight prospective studies found that women with higher blood levels of α-carotene, β-carotene, lutein and zeaxanthin, lycopene, and total carotenoids had a reduced risk of breast cancer.8 However, the findings from individual studies have varied.

Astaxanthin, which is widely distributed in the red pigment of shrimp, salmon, and crab, has been found to protect cells against oxidation and slow the proliferation of cancer cells in both the laboratory and animal studies.9

Cardiovascular Disease
The critical role inflammation plays in the development of cardiovascular disease is well established. It leads to oxidation of LDLs, which is the initial step in the development of atherosclerosis. Dietary carotenoids act as antioxidants that can prevent or reverse inflammation. An increased intake of fruits and vegetables, which are rich in carotenoids, has been associated with a reduction in several risk factors for cardiovascular disease (eg, oxidized LDLs, inflammation of vascular walls, impaired glucose metabolism).9 In addition, low blood levels of carotenoids (α-carotene, β-carotene, lutein, lycopene, zeaxanthin) have been associated with an increased risk of atherosclerotic vascular events and death from cardiovascular disease.10 Dietary and circulating lycopene have been associated with a lower risk of stroke.11 Despite the promising findings, most researchers agree that further studies are needed to sift through the findings and develop specific recommendations.

Macular Degeneration
Age-related macular degeneration (AMD) is the result of a deterioration of the retina and is most common in people aged 55 and older. Two large studies have found that carotenoid supplements of lutein and zeaxanthin may slow disease progression, which otherwise is a contributing factor to blindness.12,13 However, a beneficial effect was seen only in high-risk patients, and there's no way to know whether the supplements given provided the optimal benefit of risk reduction. Whether carotenoid supplementation lowers risk in the early stages of the disease isn't known. In addition, as with many diseases, there's a genetic component to AMD. Any benefit from supplementation may depend on an individual's genetic risk profile.14 Some studies have suggested that supplemental meso-zeaxanthin, a common metabolite of lutein and zeaxanthin, might increase benefits.15 However, some studies have found that dietary lutein or zeaxanthin alone can build macular pigment and improve visual acuity.16,17

Other Possible Benefits
Animal studies also have suggested an antiobesity benefit of fucoxanthin, a carotenoid found in edible brown seaweed. While several mechanisms have been suggested, none have been identified, and it hasn't been tested in humans.18 Intervention studies suggest a beneficial effect of supplementation with several different carotenoids for reducing the accumulation of abdominal fat.19 Studies have uncovered a possible role of β-carotene as an antioxidant defense against the sun's ultraviolet rays.20 There are also human trials suggesting that supplementing men with 4 to 8 mg of lycopene daily for three to 12 months may increase sperm count and viability and decrease DNA damage.21

Recommendations
Findings of the health benefits of consuming diets rich in carotenoids or carotenoid supplementation haven't been consistent, and experts have called for extensive, detailed research before recommendations can be made. Beta-carotene is the only carotenoid for which a recommendation has been made (3 to 6 mg/day), which is based on its ability to convert to vitamin A rather than for disease prevention. In addition, there are many more carotenoids found in foods commonly eaten that haven't been studied and may provide their own health benefits. The best advice to give to clients and patients is to stack the disease-preventing odds in their favor by increasing their intakes of the most colorful fruits and vegetables at every meal. It's as simple and as complex as that.

— Densie Webb, PhD, RD, is a freelance writer, editor, and industry consultant based in Austin, Texas.

References
1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intake for Vitamin C, Vitamin E, Selenium and Carotenoids. Washington, D.C.: National Academy Press; 2000.

2. Holick CN, Michaud DS, Stolzenberg-Solomon R, et al. Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the alpha-tocopherol, beta-carotene cohort study. Am J Epidemiol. 2002;156(6):536-547.

3. Gallicchio L, Boyd K, Matanoski G, et al. Carotenoids and the risk of developing lung cancer: a systematic review. Am J Clin Nutr. 2008;88(2):372-383.

4. Min KB, Min JY. Serum carotenoid levels and risk of lung cancer death in US adults. Cancer Sci. 2014;105(6):736-743.

5. Ilic D, Forbes KM, Hassed C. Lycopene for the prevention of prostate cancer. Cochrane Database Syst Rev. 2011;(11):CD008007.

6. Chen P, Zhang W, Wang X, et al. Lycopene and risk of prostate cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2015;94(33):e1260.

7. Gajowik A, Dobrzyńska MM. Lycopene — antioxidant with radioprotective and anticancer properties. A review. Rocz Panstw Zakl Hig. 2014;65(4):263-271.

8. Eliassen AH, Hendrickson SJ, Brinton LA, et al. Circulating carotenoids and risk of breast cancer: pooled analysis of eight prospective studies. J Natl Cancer Inst. 2012;104(24):1905-1916.

9. Zhang L, Wang H. Multiple mechanisms of anti-cancer effects exerted by astaxanthin. Mar Drugs. 2015;13(7):4310-4330.

10. Ciccone MM, Cortese F, Gesualdo M, et al. Dietary intake of carotenoids and their antioxidant and anti-inflammatory effects in cardiovascular care. Mediators Inflamm. 2013;2013:782137.

11. Li X, Xu J. Dietary and circulating lycopene and stroke risk: a meta-analysis of prospective studies. Sci Rep. 2014;4:5031.

12. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss: AREDS report no. 8. Arch Ophthalmol. 2001;119(10):1417-1436.

13. Age-Related Eye Disease Study 2 Research Group. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA. 2013;309(19):2005-2015.

14. Schmidl D, Garhöfer G, Schmetterer L. Nutritional supplements in age-related macular degeneration. Acta Ophthalmol. 2015;93(2):105-121.

15. Akuffo KO, Nolan JM, Howard AN, et al. Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration. Eye (Lond). 2015;29(7):902-912.

16. Richer SP, Stiles W, Graham-Hoffman K, et al. Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973. Optometry. 2011;82(11):667-680.

17. Johnson EJ, Neuringer M, Russell RM, Schalch W, Snodderly DM. Nutritional manipulation of primate retinas, III: effects of lutein or zeaxanthin supplements on adipose tissue and retina of xanthophyll-free monkeys. Invest Ophthalmol Vis Sci. 2005;46(2):692-702.

18. Gammone MA, D'Orazio N. Anti-obesity activity of the marine carotenoid fucoxanthin. Mar Drugs. 2015;13(4):2196-2214.

19. Bonet ML, Canas JA, Ribot J, Palou A. Carotenoids and their conversion products in the control of adipocyte function, adiposity and obesity. Arch Biochem Biophys. 2015;572:112-125.

20. Godic A, Poljšak B, Adamic M, Dahmane R. The role of antioxidants in skin cancer prevention and treatment. Oxid Med Cell Longev. 2014;2014:860479.

21. Durairajanayagam D, Agarwal A, Ong C, Prashast P. Lycopene and male infertility. Asian J Androl. 2014;16(3):420-425.