Topic of the Month
Carotenoids and health: Factors affecting bioavailability
Carotenoids are a class of fat-soluble molecules that occur naturally in many plants, including the vegetables we eat. They impart the yellow, red and orange hues to many of these foods (1). These compounds are known for their health benefits, which differ among the various carotenoid types. Some, like β-carotene, α-carotene and β-cryptoxanthin have pro-vitamin A activity, meaning they can be converted by the body into vitamin A (2). Others, like lycopene, lutein and zeaxanthin, are known for their antioxidant activity or are found in the retina of the eye (3,4). To achieve the optimal health benefit of any nutrient, it is important to understand which factors play a role in how they are taken up by the body.
Importance of bioavailability: The β-carotene and vitamin A story
Although rare in developed countries, vitamin A deficiency continues to be a serious and widespread problem throughout the world (5). The World Health Organization estimates that more than 250 million preschool-aged children suffer from vitamin A deficiency. As a result, up to half a million children become blind each year, with half dying within a year of losing their sight (6). In many of these countries, there is limited access to foods that contain pre-formed vitamin A in the form of retinol (dairy foods, egg yolk or liver). Because of this, the predominant source of vitamin A is pro-vitamin A carotenoids, such as β-carotene (7). However, controversy exists regarding the amount of vitamin A activity that can be assumed from β-carotene. As evidence of this, key scientific or regulatory bodies have issued differing guidance on the topic (Table 1).
EFSA’s recommendation uses an equivalency based on a Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) recommendation, whereas the U.S. Food and Drug Administration (FDA) uses an equivalency based on the U.S. Institute of Medicine (IOM) 2001 Dietary Reference Intake for vitamin A. The reason for the differences in scientific consensus and subsequent regulatory statements may stem from variation in reported values from the scientific literature, driven by the various factors that may influence carotenoid bioavailability (12).
Type and amount of carotenoid consumed
As one might expect, different carotenoids have been shown to have varying bioavailability, partly due to molecular structure but also to their respective absorption mechanisms (13). Generally, the higher the dose of carotenoid, the lower the percentage that’s absorbed. In studies where pure β-carotene in oil has been administered at “physiological” doses (about 500 mcg), around half has been found to be absorbed (14). However, where larger doses were tested (about 15 mg), only about 10-15% of the dose was absorbed (15). Similar trends have been observed for other carotenoids (16).
Physical structure of the carotenoid in the food
The way carotenoids are deposited into the cell of a plant as it grows also has potential to affect carotenoid bioavailability. The crystalline structure of the carotenoid, or other components within the plant cell, may inhibit their access for intestinal absorption. This may differ among plant species (17), including biofortified crops (18). IOM’s 6:1 equivalence of pure (supplemental) to dietary β-carotene was established in the context of several studies where β-carotene in a plant food matrix was compared to pure β-carotene in oil, consumed as a supplement with meals (19,20), or included in a food matrix such as a baked wafer (21) or salad dressing (13,22). However, it’s important to recognize that the results of those, and more recently published studies, vary considerably.
Degree of food processing
Contrary to what we might expect, cooking foods may actually increase carotenoid absorption. Although some degradation can occur at high temperatures, heat treatment of plant tissues can substantially improve bioavailability, possibly by disrupting plant cell walls or other barriers to the release and absorption of carotenoids (23). For example, increased absorption of lycopene has been observed from tomato paste compared to raw tomatoes (24,25).
Presence of other nutrients
Other components of a food or meal can also influence bioavailability. The presence of dietary fat has been shown to improve β-carotene absorption. The addition of full-fat salad dressing was shown to dramatically improve carotenoid absorption compared to low fat or fat free dressing in one study (26). Fats from other foods such as avocado can also improve carotenoid absorption (27). The lutein found in egg yolk has been shown to be highly bioavailable (28) and the consumption of eggs in combination with raw vegetables has been shown to help increase the absorption of carotenoids from the vegetables.
Differences among individuals
Regardless of the dietary form in which carotenoids are consumed, physiological differences among individuals can also influence carotenoid absorption. There is increasing recognition that genetic factors may play a role in the bioavailability of carotenoids. See the March Topic of the Month for a perspective on how differences in the β-carotene conversion enzyme BCMO1 may influence individual responses. Individuals with certain genetic variants of the BCMO1 gene may be more prone to vitamin A deficiency and should assure that they are consuming adequate amounts of pre-formed vitamin A (29). A low vitamin A status in the body can result in an increased conversion of β-carotene to retinol (30). Body weight has been associated with serum carotenoid levels (31), and vitamin A deficiency has been observed in bariatric surgery patients, due to the changes in the small intestine (32). Other mechanisms may come into play for the xanthophylls. Recent research suggests that individual differences in lipoprotein metabolism may influence the delivery of lutein and zeaxanthin to the retina as they are transported on LDL and HDL particles (33).
Getting the most out of our carotenoids
So, given these variables, how do we assure that we are getting the most out of the carotenoids in our diet? Of course, we can’t control all the factors described above. However, there are several rules of thumb to consider:
- Eat a colorful diet: Eating green, yellow, orange and red vegetables and fruits on a regular basis will boost your carotenoid intake.
- Cook it up: Heat processing can help maximize carotenoid release.
- Don’t fear some fat: Cooking with oil is a great way to promote the absorption of fat soluble carotenoids and other fat soluble vitamins from vegetables.
- Supplement a meal: When taking a supplement, consume it with a meal. This is not only good advice for carotenoids, but for other nutrients as well.
- Namitha KK, Negi PS. Chemistry and Biotechnology of Carotenoids. Crit Rev Food Sci Nutr. 2010;50:728–60. http://dx.doi.org/10.1080/10408398.2010.499811
- Weber D, Grune T. The contribution of β-carotene to vitamin A supply of humans. Mol Nutr Food Res. 2012;56:251–8. http://dx.doi.org/10.1002/mnfr.201100230
- Johnson EJ. Role of lutein and zeaxanthin in visual and cognitive function throughout the lifespan. Nutr Rev. 2014;72:605–12. https://doi.org/10.1111/nure.12133
- Rowles JL, Ranard KM, Smith JW, An R, Erdman JW. Increased dietary and circulating lycopene are associated with reduced prostate cancer risk: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2017; http://dx.doi.org/10.1038/pcan.2017.25
- World Health Organization WH. Global prevalence of vitamin A deficiency in populations at risk 1995-2005: WHO global database on vitamin A deficiency. 2009 [cited 2017 May 3]; Available from: http://apps.who.int/iris/handle/10665/44110
- World Health Organization. WHO Global Database on Vitamin A Deficiency [Internet]. WHO. [cited 2017 May 3]. Available from: http://www.who.int/vmnis/database/vitamina/en/
- Haskell MJ. The challenge to reach nutritional adequacy for vitamin A: β-carotene bioavailability and conversion—evidence in humans. Am J Clin Nutr. 2012;96:1193S–1203S. http://dx.doi.org/10.3945/ajcn.112.034850
- EFSA Panel on Dietetic Products, Nutrition, and Allergies. Scientific Opinion on Dietary Reference Values for vitamin A: Dietary Reference Values for vitamin A. EFSA J. 2015;13:4028. http://dx.doi.org/10.2903/j.efsa.2015.4028
- FAO/WHO. Human Vitamin and Mineral Requirements: Report of a joint FAO/WHO expert consultation. Bangkok, Thailand; 2002. http://www.fao.org/docrep/004/y2809e/y2809e00.htm
- U.S. FDA. e-CFR: Title 21: Food and Drugs PART 101—FOOD LABELING Subpart A—General Provisions [Internet]. Electronic Code of Federal Regulations 2016. Available from: https://www.ecfr.gov/cgi-bin/text-idx?SID=912cd4e9fb8265e4e149e67b589b01f2&mc=true&node=se21.2.101_19&rgn=div8
- U.S. Institute of Medicine, editor. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc: a report of the Panel on Micronutrients ... and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes, Food and Nutrition Board, Institute of Medicine. Washington, D.C: National Academy Press; 2001. 773 p. https://www.nap.edu/read/10026/chapter/6
- Fernández-García E, Carvajal-Lérida I, Jarén-Galán M, Garrido-Fernández J, Pérez-Gálvez A, Hornero-Méndez D. Carotenoids bioavailability from foods: From plant pigments to efficient biological activities. Food Res Int. 2012;46:438–50. https://doi.org/10.1016/j.foodres.2011.06.007
- van het Hof KH, Brouwer IA, West CE, Haddeman E, Steegers-Theunissen RP, van Dusseldorp M, Weststrate JA, Eskes TK, Hautvast JG. Bioavailability of lutein from vegetables is 5 times higher than that of β-carotene. Am J Clin Nutr. 1999;70:261–268. http://ajcn.nutrition.org/content/70/2/261
- Ho CC, Moura FF de, Kim S-H, Burri BJ, Clifford AJ. A Minute Dose of 14C-β-Carotene Is Absorbed and Converted to Retinoids in Humans. J Nutr. 2009;139:1480–6. http://dx.doi.org/10.3945/jn.109.105114
- Vliet T van, Schreurs WH, Berg H van den. Intestinal beta-carotene absorption and cleavage in men: response of beta-carotene and retinyl esters in the triglyceride-rich lipoprotein fraction after a single oral dose of beta-carotene. Am J Clin Nutr. 1995;62:110–6. http://ajcn.nutrition.org/content/62/1/110
- Sherry CL, Oliver JS, Renzi LM, Marriage BJ. Lutein Supplementation Increases Breast Milk and Plasma Lutein Concentrations in Lactating Women and Infant Plasma Concentrations but Does Not Affect Other Carotenoids. J Nutr. 2014;144:1256–63. http://dx.doi.org/10.3945/jn.114.192914
- Schweiggert RM, Kopec RE, Villalobos-Gutierrez MG, Högel J, Quesada S, Esquivel P, Schwartz SJ, Carle R. Carotenoids are more bioavailable from papaya than from tomato and carrot in humans: a randomised cross-over study. Br J Nutr. 2014;111:490–8. https://doi.org/10.1017/S0007114513002596
- Li S, Nugroho A, Rocheford T, White WS. Vitamin A equivalence of the beta-carotene in beta-carotene-biofortified maize porridge consumed by women. Am J Clin Nutr. 2010;92:1105–12. http://dx.doi.org/10.3945/ajcn.2010.29802
- Micozzi MS, Brown ED, Edwards BK, Bieri JG, Taylor PR, Khachik F, Beecher GR, Smith JC. Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am J Clin Nutr. 1992;55:1120–1125. http://ajcn.nutrition.org/content/55/6/1120
- Törrönen R, Lehmusaho M, Häkkinen S, Hänninen O, Mykkänen H. Serum β-carotene response to supplementation with raw carrots, carrot juice or purified β-carotene in healthy non-smoking women. Nutr Res. 1996;16:565–75. https://doi.org/10.1016/0271-5317(96)00035-8
- de Pee S, West CE, Hautvast JGAJ, Muhilal, Karyadi D, West CE. Lack of improvement in vitamin A status with increased consumption of dark-green leafy vegetables. The Lancet. 1995;346:75–81. https://doi.org/10.1016/S0140-6736(95)92111-7
- Castenmiller JJ, West CE, Linssen JP, van het Hof KH, Voragen AG. The food matrix of spinach is a limiting factor in determining the bioavailability of β-carotene and to a lesser extent of lutein in humans. J Nutr. 1999;129:349–355. http://jn.nutrition.org/content/129/2/349
- van het Hof KH, West CE, Weststrate JA, Hautvast JGAJ. Dietary Factors That Affect the Bioavailability of Carotenoids. J Nutr. 2000;130:503–6. http://jn.nutrition.org/content/130/3/503
- Gärtner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr. 1997;66:116–22. http://ajcn.nutrition.org/content/66/1/116
- Böhm V, Bitsch R. Intestinal absorption of lycopene from different matrices and interactions to other carotenoids, the lipid status, and the antioxidant capacity of human plasma. Eur J Nutr. 1999;38:118–125. http://dx.doi.org/10.1007/s003940050052
- Brown MJ, Ferruzzi MG, Nguyen ML, Cooper DA, Eldridge AL, Schwartz SJ, White WS. Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am J Clin Nutr. 2004;80:396–403. http://ajcn.nutrition.org/content/80/2/396
- Kopec RE, Cooperstone JL, Schweiggert RM, Young GS, Harrison EH, Francis DM, Clinton SK, Schwartz SJ. Avocado Consumption Enhances Human Postprandial Provitamin A Absorption and Conversion from a Novel High–β-Carotene Tomato Sauce and from Carrots. J Nutr. 2014;144:1158–66. http://dx.doi.org/10.3945/jn.113.187674
- Goodrow EF, Wilson TA, Houde SC, Vishwanathan R, Scollin PA, Handelman G, Nicolosi RJ. Consumption of one egg per day increases serum lutein and zeaxanthin concentrations in older adults without altering serum lipid and lipoprotein cholesterol concentrations. J Nutr. 2006;136:2519–2524. http://jn.nutrition.org/content/136/10/2519
- Borel P, Desmarchelier C. Genetic Variations Associated with Vitamin A Status and Vitamin A Bioavailability. Nutrients. 2017;9:246. http://dx.doi.org/10.3390/nu9030246
- Tanumihardjo SA. Factors influencing the conversion of carotenoids to retinol: bioavailability to bioconversion to bioefficacy. Int J Vitam Nutr Res. 2002;72:40–45. DOI: http://dx.doi.org/10.1024/0300-9818.104.22.168
- Gunanti IR, Marks GC, Al-Mamun A, Long KZ. Low serum concentrations of carotenoids and vitamin E are associated with high adiposity in Mexican-American children. J Nutr. 2014;144:489–95. http://dx.doi.org/10.3945/jn.113.183137
- Fok JS, Li JYZ, Yong TY. Visual deterioration caused by vitamin A deficiency in patients after bariatric surgery. Eat Weight Disord. 2012;17:e144-146. http://dx.doi.org/10.1007/BF03325340
- Merle, B.M.J., Maubaret, C., Korobelnik, J.-F., Delyfer, M.-N., Rougier, M.-B., Lambert, J.-C., Amouyel, P., Malet, F., Goff, M.L., Dartigues, J.-F., et al. Association of HDL-Related Loci with Age-Related Macular Degeneration and Plasma Lutein and Zeaxanthin: the Alienor Study. PLOS ONE. 2013;8:e79848. https://doi.org/10.1371/journal.pone.0079848