Influence of phytosterol and phytostanol food supplementation on plasma liposoluble vitamins and provitamin A carotenoid levels in humans: An updated review of the evidence

Critical Reviews in Food Science and Nutrition

Volumn 57, Issue 9, 2017, Pages 1906-1921

  Fardet, Anthony ^a   Morise, Anne ^b   Kalonji, Esther ^b   Margaritis, Irène ^b   Mariotti, François ^c  

^a INRA and University of Auvergne   (France)

^b FRENCH AGENCY FOR FOOD   (France)

^c CENTRE MAURICE HALBWACHS   (France)

Author keywords

cardiovascular disease risk; intervention studies; liposoluble vitamins; Phytosterol and phytostanol enriched foods; provitamin A carotenoids

Indexed keywords

ALCOHOLS; BIOCHEMISTRY; CHOLESTEROL; FOOD ADDITIVES; PIGMENTS; PLASMA SHOCK WAVES; RISK PERCEPTION;

BIOAVAILABILITY STUDY; CARDIO-VASCULAR DISEASE; CHOLESTEROL ABSORPTION; ENRICHED FOOD; FRUITS AND VEGETABLES; INTERVENTION STUDIES; PLASMA CONCENTRATION; PROVITAMIN A;

VITAMINS;

CAROTENOID; PHYTOSTEROL; VITAMIN;

BLOOD; CHEMISTRY; DIETARY SUPPLEMENT; FOOD ANALYSIS; HUMAN;

CAROTENOIDS; DIETARY SUPPLEMENTS; FOOD ANALYSIS; HUMANS; PHYTOSTEROLS; VITAMINS;

EID: 85014952657     PISSN: 10408398     EISSN: 15497852     Source Type: Journal    
DOI: 10.1080/10408398.2015.1033611     Document Type: Article

References (85)

1. Agence Nationale de Sécurité Sanitaire de l'Alimentation. Avis lié à l'Evaluation du risque et du bénéfice liés à la consommation de produits alimentaires enrichis en phytostérols ou en phytostanols (Saisine n°2010-SA-0057 «Phytostérols») 2014; Maison-Alfort. p. 41–46.
2. Amundsen, A. L., Ntanios, F., van der Put, N., and Ose, L., (2004). Long-term compliance and changes in plasma lipids, plant sterols and carotenoids in children and parents with FH consuming plant sterol ester-enriched spread. Eur. J. Clin. Nutr. 58:1612–1620.
3. Amundsen, Å. L., Ose, L., Nenseter, M. S., and Ntanios, F. Y., (2002). Plant sterol ester–enriched spread lowers plasma total and LDL cholesterol in children with familial hypercholesterolemia. Am. J. Clin. Nutr. 76:338–344.
4. Andersson, A., Karlstrom, B., Mohsen, R., and Vessby, B., (1999). Cholesterol-lowering effects of a stanol ester-containing low-fat margarine used in conjunction with a strict lipid-lowering diet. Eur. Heart J. Suppl. 1:S80–S90.
5. Bañuls, C., Martínez-Triguero, M. L., López-Ruiz, A., Morillas, C., Lacomba, R., Víctor, V. M., Rocha, M., and Hernández-Mijares, A., (2010). Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols. J. Nutr. Biochem. 21:881–886.
6. Borel, P., (2003). Factors affecting intestinal absorption of highly lipophilic food microconstituents (fat-soluble vitamins, carotenoids and phytosterols). Clin. Chem. Lab. Med. 41:979–994.
7. Borel, P., Grolier, P., Armand, M., Partier, A., Lafont, H., Lairon, D., and Azais-Braesco, V., (1996). Carotenoids in biological emulsions:Solubility, surface-to-core distribution, and release from lipid droplets. J. Lipid Res. 37:250–261.
8. Borel, P., Moussa, M., Reboul, E., Lyan, B., Defoort, C., Vincent-Baudry, S., Maillot, M., Gastaldi, M., Darmon, M., Portugal, H., Lairon, D., and Planells, R., (2009). Human fasting plasma concentrations of vitamin E and carotenoids, and their association with genetic variants in apo C-III, cholesteryl ester transfer protein, hepatic lipase, intestinal fatty acid binding protein and microsomal triacylglycerol transfer protein. Brit. J. Nutr. 101:680–687.
9. Brufau, G., Quílez, J., Angel Canela, M., Salas-Salvadó, J., Bulló, M., and Rafecas, M., (2004). Evaluation of lipid oxidation after ingestion of bakery products enriched with phytosterols, β-carotene and α-tocopherol. Clin. Nutr. 23:1390–1397.
10. Buijsse, B., Feskens, E. J., Schlettwein-Gsell, D., Ferry, M., Kok, F. J., Kromhout, D., and De Groot, L. C., (2005). Plasma carotene and alpha-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly:The survey in Europe on nutrition and the elderly, a concerted action (SENECA). Am. J. Clin. Nutr. 82:879–886.
11. Chen, S., Judd, J., Kramer, M., Meijer, G., Clevidence, B., and Baer, D., (2009). Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol. Lipids. 44:273–281.
12. Christiansen, L. I., Lahteenmaki, P. L. A., Mannelin, M. R., Seppanen-Laakso, T. E., Hiltunen, R. V. K., and Yliruusi, J. K., (2001). Cholesterol-lowering effect of spreads enriched with microcrystal line plant sterols in hypercholesterolemic subjects. Eur. J. Nutr. 40:66–73.
13. Clifton, P. M., Noakes, M., Ross, D., Fassoulakis, A., Cehun, M., and Nestel, P., (2004). High dietary intake of phytosterol esters decreases carotenoids and increases plasma plant sterol levels with no additional cholesterol lowering. J. Lipid Res. 45:1493–1499.
14. Colgan, H. A., Floyd, S., Noone, E. J., Gibney, M. J., and Roche, H. M., (2004). Increased intake of fruit and vegetables and a low-fat diet, with and without low-fat plant sterol-enriched spread consumption:Effects on plasma lipoprotein and carotenoid metabolism. J. Human Nutr. Diet. 17:561–569.
15. Davidson, M. H., Maki, K. C., Umporowicz, D. M., Ingram, K. A., Dicklin, M. R., Schaefer, E., Lane, R. W., McNamara, J. R., Ribaya-Mercado, J. D., Perrone, G., Robins, S. J., and Franke, W. C., (2001). Safety and tolerability of esterified phytosterols administered in reduced-fat spread and salad dressing to healthy adult men and women. J. Am. Coll. Nutr. 20:307–319.
16. De Jong, A., Plat, J., Bast, A., Godschalk, R. W. L., Basu, S., and Mensink, R. P., (2008). Effects of plant sterol and stanol ester consumption on lipid metabolism, antioxidant status and markers of oxidative stress, endothelial function and low-grade inflammation in patients on current statin treatment. Eur. J. Clin. Nutr. 62:263–273.
17. Devaraj, S., Autret, B. C., and Jialal, I., (2006). Reduced-calorie orange juice beverage with plant sterols lowers C-reactive protein concentrations and improves the lipid profile in human volunteers. Am. J. Clin. Nutr. 84:756–761.
18. EFSA Panel on Dietetic Products, Nutrition and Allergies (2012). Scientific opinion of the panel on dietetic products, nutrition and allergies on a request from Unilever PLC and Unilever NV, related to the scientific substantitation of a health claim related to 3 g/day plant sterols/stanols and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 19 of regulation (EC) N° 1924/2006. EFSA J. 10:2693, pg. 4.
19. Eliassen, A. H., Hendrickson, S. J., Brinton, L. A., Buring, J. E., Campos, H., Dai, Q., Dorgan, J. F., Franke, A. A., Gao, Y. T., Goodman, M. T., Hallmans, G., Helzlsouer, K. J., Hoffman-Bolton, J., Hulteen, K., Sesso, H. D., Sowell, A. L., Tamimi, R. M., Toniolo, P., Wilkens, L. R., Winkvist, A., Zeleniuch-Jacquotte, A., Zheng, W., and Hankinson, S. E., (2012). Circulating carotenoids and risk of breast cancer:Pooled analysis of eight prospective studies. J. Natl. Cancer Inst. 104:1905–1916.
20. European Commission - Health & Consumer Protection Directorate-General (2000a). Décision de la Commission du 24 juillet 2000 relative à l'autorisation de mise sur le marché de « matières grasses à tartiner enrichies aux esters de phytostérol » en tant que nouvel aliment ou nouvel ingrédient alimentaire, en application du règlement (CE) n° 258/97 du Parlement européen et du Conseil [notifiée sous le numéro C(2000) 2121]. Off. J. Eur. Comm. L200:59–60.
21. European Commission - Health & Consumer Protection Directorate-General (2000b). Opinion of the Scientific Committee on Food on a Request for the Safety Assessment of the Use of Phytosterol Esters in Yellow Fat Spreads. THE COMMISSION OF THE EUROPEAN COMMUNITIES - Directorate B - Scientific Health Opinions - Unit B3 - Management of Scientific Committees II. SCF/CS/NF/DOS/1 FINAL. Bruxelles, Belgium. Available from http://ec.europa.eu/food/fs/sc/scf/out56_en.pdf.
22. Gaziano, J. M., Manson, J. E., Branch, L. G., Colditz, G. A., Willett, W. C., and Buring, J. E., (1995). A prospective study of consumption of carotenoids in fruits and vegetables and decreased cardiovascular mortality in the elderly. Ann. Epidemiol. 5:255–260.
23. Goncalves, A., Bott, R., Coméra, C., Gleize, B., Nowicki, M., Amiot, M.-J., Lairon, D., Borel, P., and Reboul, E., (2010). Les phytostérols peuvent interagir avec l'absorption intestinale de la vitamine D en diminuant son incorporation micellaire et en entrant en compétition pour son captage entérocytaire via NPC1L1. Nutr. Clin. Métabol. 24:44.
24. Goyal, A., Terry, M. B., and Siegel, A. B., (2013). Serum antioxidant nutrients, vitamin A, and mortality in U.S. adults. Cancer Epidemiol. Biomark. Prev. 22:2202–2211.
25. Granado-Lorencio, F., Donoso-Navarro, E., Manuel Sanchez-Siles, L., Blanco-Navarro, I., and Perez-Sacristan, B., (2011). Bioavailability of beta-cryptoxanthin in the presence of phytosterols:In vitro and in vivo Studies. J. Agric. Food Chem. 59:11819–11824.
26. Gylling, H., Hallikainen, M., Nissinen, M. J., and Miettinen, T. A., (2010). The effect of a very high daily plant stanol ester intake on serum lipids, carotenoids, and fat-soluble vitamins. Clin. Nutr. 29:112–118.
27. Gylling, H., and Miettinen, T. A., (1999). Cholesterol reduction by different plant stanol mixtures and with variable fat intake. Metabolism. 48:575–580.
28. Gylling, H., Puska, P., Vartiainen, E., and Miettinen, T. A., (1999). Retinol, vitamin D, carotenes and alpha-tocopherol in serum of a moderately hypercholesterolemic population consuming sitostanol ester margarine. Atherosclerosis. 145:279–285.
29. Hallikainen, M. A., Sarkkinen, E. S., Gylling, H., Erkkila, A. T., and Uusitupa, M. I. J., (2000). Comparison of the effects of plant sterol ester and plant stanol ester-enriched margarines in lowering serum cholesterol concentrations in hypercholesterolaemic subjects on a low-fat diet. Eur. J. Clin. Nutr. 54:715–725.
30. Hallikainen, M. A., Sarkkinen, E. S., and Uusitupa, M. I. J., (1999). Effects of low-fat stanol ester enriched margarines on concentrations of serum carotenoids in subjects with elevated serum cholesterol concentrations. Eur. J. Clin. Nutr. 53:966–969.
31. Hallikainen, M. A., and Uusitupa, M. I., (1999). Effects of 2 low-fat stanol ester–containing margarines on serum cholesterol concentrations as part of a low-fat diet in hypercholesterolemic subjects. Am. J. Clin. Nutr. 69:403–410.
32. Hansel, B., Nicolle, C., Lalanne, F., Tondu, F., Lassel, T., Donazzolo, Y., Ferrières, J., Krempf, M., Schlienger, J.-L., Verges, B., Chapman, M. J., and Bruckert, E., (2007). Effect of low-fat, fermented milk enriched with plant sterols on serum lipid profile and oxidative stress in moderate hypercholesterolemia. Am. J. Clin. Nutr. 86:790–796.
33. Heggen, E., Granlund, L., Pedersen, J. I., Holme, I., Ceglarek, U., Thiery, J., Kirkhus, B., and Tonstad, S., (2010). Plant sterols from rapeseed and tall oils:Effects on lipids, fat-soluble vitamins and plant sterol concentrations. Nutr. Metabol. Cardiovasc. Dis. 20:258–265.
34. Hendriks, H. F. J., Brink, E. J., Meijer, G. W., Princen, H. M. G., and Ntanios, F. Y., (2003). Safety of long-term consumption of plant sterol esters-enriched spread. Eur. J. Clin. Nutr. 57:681–692.
35. Hendriks, H. F. J., Weststrate, J. A., van Vliet, T., and Meijer, G. W., (1999). Spreads enriched with three different levels of vegetable oil sterols and the degree of cholesterol lowering in normocholesterolaemic and mildly hypercholesterolaemic subjects. Eur. J. Clin. Nutr. 53:319–327.
36. Hernández-Mijares, A., Bañuls, C., Rocha, M., Morillas, C., Martínez-Triguero, M. L., Víctor, V. M., Lacomba, R., Alegría, A., Barberá, R., Farré, R., and Lagarda, M. J., (2010). Effects of phytosterol ester-enriched low-fat milk on serum lipoprotein profile in mildly hypercholesterolaemic patients are not related to dietary cholesterol or saturated fat intake. Brit. J. Nutr. 104:1018–1025.
37. Holick, C. N., Michaud, D. S., Stolzenberg-Solomon, R., Mayne, S. T., Pietinen, P., Taylor, P. R., Virtamo, J., and Albanes, D., (2002). Dietary carotenoids, serum beta-carotene, and retinol and risk of lung cancer in the Alpha-Tocopherol, Beta-Carotene Cohort Study. Am. J. Epidemiol. 156:536–547.
38. Homma, Y., Ikeda, I., Ishikawa, T., Tateno, M., Sugano, M., and Nakamura, H., (2003). Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread:A randomized, placebo-controlled trial. Nutrition. 19:369–374.
39. Ito, Y., Kurata, M., Suzuki, K., Hamajima, N., Hishida, H., and Aoki, K., (2006a). Cardiovascular disease mortality and serum carotenoid levels:A Japanese population-based follow-up study. J. Epidemiol. 16:154–160.
40. Ito, Y., Suzuki, K., Ishii, J., Hishida, H., Tamakoshi, A., Hamajima, N., and Aoki, K., (2006b). A population-based follow-up study on mortality from cancer or cardiovascular disease and serum carotenoids, retinol and tocopherols in Japanese inhabitants. Asian Pac. J. Cancer Prev. 7:533–546.
41. Judd, J. T., Baer, D. J., Chen, S. C., Clevidence, B. A., Muesing, R. A., Kramer, M., and Meijer, G. W., (2002). Plant sterol esters lower plasma lipids and most carotenoids in mildly hypercholesterolemic adults. Lipids. 37:33–42.
42. Kaffe, E., Salakidou, C., Menounou, I., Challa, A., and Moulas, A. N., (2012). Effect of plant sterols on vitamin D absorption. Ann. Nutr. Metabol. 60:138–138.
43. Katan, M. B., Grundy, S. M., Jones, P., Law, M., Miettinen, T., Paoletti, R., and Stresa Workshop, P., (2003). Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clinic Proc. 78:965–978.
44. Kohlmeier, L., and Hastings, S. B., (1995). Epidemiologic evidence of a role of carotenoids in cardiovascular disease prevention. Am. J. Clin. Nutr. 62:1370S–1376S.
45. Korpela, R., Tuomilehto, J., Hogstrom, P., Seppo, L., Piironen, V., Salo-Vaananen, P., Toivo, J., Lamberg-Allardt, C., Karkkainen, M., Outila, T., Sundvall, J., Vilkkila, S., and Tikkanen, M. J., (2006). Safety aspects and cholesterol-lowering efficacy of low fat dairy products containing plant sterols. Eur. J. Clin. Nutr. 60:633–642.
46. Kritchevsky, D., and Chen, S. C., (2005). Phytosterols - Health benefits and potential concerns:A review. Nutr. Res. 25:413–428.
47. Kritchevsky, S. B., (1999). Beta-carotene, carotenoids and the prevention of coronary heart disease. J. Nutr. 129:5–8.
48. Kritchevsky, S. B., Tell, G. S., Shimakawa, T., Dennis, B., Li, R., Kohlmeier, L., Steere, E., and Heiss, G., (1998). Provitamin A carotenoid intake and carotid artery plaques:The Atherosclerosis Risk in Communities Study. Am. J. Clin. Nutr. 68:726–733.
49. Lidebjer, C., Leanderson, P., Ernerudh, J., and Jonasson, L., (2007). Low plasma levels of oxygenated carotenoids in patients with coronary artery disease. Nutr. Metab. Cardiovasc. Dis. 17:448–456.
50. Lux, O., and Naidoo, D., (1994). Biological variation of beta-carotene. Nutr. Res. 14:693–698.
51. Maki, K. C., Davidson, M. H., Umporowicz, D. M., Schaefer, E. J., Dicklin, M. R., Ingram, K. A., Chen, S., McNamara, J. R., Gebhart, B. W., Ribaya-Mercado, J. D., Perrone, G., Robins, S. J., and Franke, W. C., (2001). Lipid responses to plant-sterol-enriched reduced-fat spreads incorporated into a National Cholesterol Education Program Step I diet. Am. J. Clin. Nutr. 74:33–43.
52. Mensink, R. P., de Jong, A., Lutjohann, D., Haenen, G. R., and Plat, J., (2010). Plant stanols dose-dependently decrease LDL-cholesterol concentrations, but not cholesterol-standardized fat-soluble antioxidant concentrations, at intakes up to 9 g/d. Am. J. Clin. Nutr. 92:24–33.
53. Mensink, R. P., Ebbing, S., Lindhout, M., Plat, J., and van Heugten, M. M. A., (2002). Effects of plant stanol esters supplied in low-fat yoghurt on serum lipids and lipoproteins, non-cholesterol sterols and fat soluble antioxidant concentrations. Atherosclerosis. 160:205–213.
54. Miyashita, T., Mori, M., Tagushi, T., Sagara, M., Birt, C., Inakuma, T., and Yamori, Y., (2011). Associations of carotenoids with coronary heart disease risks in Scottish middle-aged males and females. Ann. Nutr. Metabol. 58:168–169.
55. Morris, D. L., Kritchevsky, S. B., and Davis, C. E., (1994). Serum carotenoids and coronary heart disease. The Lipid Research Clinics Coronary Primary Prevention Trial and Follow-up Study. JAMA. 272:1439–1441.
56. Musa-Veloso, K., Poon, T. H., Elliot, J. A., and Chung, C., (2011). A comparison of the LDL- cholesterol lowering efficacy of plant stanols and plant sterols over a continuous dose range:Results of a meta-analysis of randomized, placebo-controlled trials. Prostaglandins Leukot. Essent. Fatty Acids. 85:9–28.
57. Nestel, P., Cehun, M., Pomeroy, S., Abbey, M., and Weldon, G., (2001). Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. Eur. J. Clin. Nutr. 55:1084–1090.
58. Nguyen, T. T., Dale, L. C., von Bergmann, K., and Croghan, I. T., (1999). Cholesterol-lowering effect of stanol ester in a US population of mildly hypercholesterolemic men and women:A randomized controlled trial. Mayo Clin. Proc. 74:1198–1206.
59. Noakes, M., Clifton, P., Ntanios, F., Shrapnel, W., Record, I., and McInerney, J., (2002). An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am. J. Clin. Nutr. 75:79–86.
60. Ntanios, F. Y., and Duchateau, G. S. M. J. E., (2002). A healthy diet rich in carotenoids is effective in maintaining normal blood carotenoid levels during the daily use of plant sterol-enriched spreads. Int. J. Vitam. Nutr. Res. 72:32–39.
61. Ntanios, F. Y., Homma, Y., and Ushiro, S., (2002). A spread enriched with plant sterol-esters lowers blood cholesterol and lipoproteins without affecting vitamins A and E in normal and hypercholesterolemic Japanese men and women. J. Nutr. 132:3650–3655.
62. Palace, V. P., Khaper, N., Qin, Q. I., and Singal, P. K., (1999). Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radic. Biol. Med. 26:746–761.
63. Petrogianni, M., Kanellakis, S., Moschonis, G., and Manios, Y., (2014). Fortification of vitamin A in a phytosterol enriched milk maintains plasma beta-carotene levels. J. Food Sci. Technol.-Mysore. 51:196–199.
64. Plat, J., and Mensink, R. P., (2000). Vegetable oil based versus wood based stanol ester mixtures:Effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis. 148:101–112.
65. Plat, J., and Mensink, R. P., (2001). Effects of diets enriched with two different plant stanol ester mixtures on plasma ubiquinol-10 and fat-soluble antioxidant concentrations. Metabolism. 50:520–529.
66. Plat, J., van Onselen, E. N., van Heugten, M. M., and Mensink, R. P., (2000). Effects on serum lipids, lipoproteins and fat soluble antioxidant concentrations of consumption frequency of margarines and shortenings enriched with plant stanol esters. Eur. J. Clin. Nutr. 54:671–677.
67. Polagruto, J. A., Wang-Polagruto, J. F., Braun, M. M., Lee, L., Kwik-Uribe, C., and Keen, C. L., (2006). Cocoa flavanol-enriched snack bars containing phytosterols effectively lower total and low-density lipoprotein cholesterol levels. J. Am. Diet. Assoc. 106:1804–1813.
68. Quílez, J., Rafecas, M., Brufau, G., García-Lorda, P., Megías, I., Bulló, M., Ruiz, J. A., and Salas-Salvadó, J., (2003). Bakery products enriched with phytosterol esters, α-tocopherol and β-carotene decrease plasma LDL-cholesterol and maintain plasma β-carotene concentrations in normocholesterolemic men and women. J. Nutr. 133:3103–3109.
69. Raeini-Sarjaz, M., Ntanios, F. Y., Vanstone, C. A., and Jones, P. J. H., (2002). No changes in serum fat-soluble vitamin and carotenoid concentrations with the intake of plant sterol/stanol esters in the context of a controlled diet. Metabolism. 51:652–656.
70. Ras, R. T., Hiemstra, H., Lin, Y., Vermeer, M. A., Duchateau, G. S. M. J. E., and Trautwein, E. A., (2013). Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations - A meta-analysis of randomized controlled studies. Atherosclerosis. 230:336–346.
71. Relas, H., Gylling, H., and Miettinen, T. A., (2001). Acute effect of dietary stanyl ester dose on post-absorptive α-tocopherol, β-carotene, retinol and retinyl palmitate concentrations. Brit. J. Nutr. 85:141–147.
72. Ribaya-Mereado, J. D., and Blumberg, J. B., (2004). Lutein and zeaxanthin and their potential roles in disease prevention. J. Am. Coll. Nutr. 23:567S–587S.
73. Richelle, M., Enslen, M., Hager, C., Groux, M., Tavazzi, I., Godin, J.-P., Berger, A., Métairon, S., Quaile, S., Piguet-Welsch, C., Sagalowicz, L., Green, H., and Fay, L. B., (2004). Both free and esterified plant sterols reduce cholesterol absorption and the bioavailability of β-carotene and α-tocopherol in normocholesterolemic humans. Am. J. Clin. Nutr. 80:171–177.
74. Rocha, M., Banuls, C., Bellod, L., Jover, A., Victor, V. M., and Hernandez-Mijares, A., (2011). A review on the role of phytosterols:New insights into cardiovascular risk. Curr. Pharm. Design. 17:4061–4075.
75. Sanchez-Muniz, F. J., Maki, K. C., Schaefer, E. J., and Ordovas, J. M., (2009). Serum lipid and antioxidant responses in hypercholesterolemic men and women receiving plant sterol esters vary by apolipoprotein E genotype. J. Nutr. 139:13–19.
76. Sesso, H. D., Buring, J. E., Norkus, E. P., and Gaziano, J. M., (2004). Plasma lycopene, other carotenoids, and retinol and the risk of cardiovascular disease in women. Am. J. Clin. Nutr. 79:47–53.
77. Sialvera, T.-E., Koutelidakis, A. E., Richter, D. J., Yfanti, G., Kapsokefalou, M., Micha, R., Goumas, G., Diamantopoulos, E., and Zampelas, A., (2013). Phytosterol supplementation does not affect plasma antioxidant capacity in patients with metabolic syndrome. Int. J. Food Sci. Nutr. 64:21–27.
78. Soderholm, P. P., Alfthan, G., Koskela, A. H., Adlercreutz, H., and Tikkanen, M. J., (2012). The effect of high-fiber rye bread enriched with nonesterified plant sterols on major serum lipids and apolipoproteins in normocholesterolemic individuals. Nutr. Metab. Cardiovasc. Dis. 22:575–582.
79. Tammi, A., Ronnemaa, T., Gylling, H., Rask-Nissila, L., Viikari, J., Tuominen, J., Pulkki, K., and Simell, O., (2000). Plant stanol ester margarine lowers serum total and low-density lipoprotein cholesterol concentrations of healthy children:The STRIP project. J. Pediatr. 136:503–510.
80. Thomsen, A. B., Hansen, H. B., Christiansen, C., Green, H., and Berger, A., (2004). Effect of free plant sterols in low-fat milk on serum lipid profile in hypercholesterolemic subjects. Eur. J. Clin. Nutr. 58:860–870.
81. Tuomilehto, J., Tikkanen, M. J., Hogstrom, P., Keinanen-Kiukaanniemi, S., Piironen, V., Toivo, J., Salonen, J. T., Nyyssonen, K., Stenman, U. H., Alfthan, H., and Karppanen, H., (2009). Safety assessment of common foods enriched with natural nonesterified plant sterols. Eur. J. Clin. Nutr. 63:684–691.
82. Volpe, R., Niittynen, L., Korpela, R., Sirtori, C., Bucci, A., Fraone, N., and Pazzucconi, F., (2001). Effects of yoghurt enriched with plant sterols on serum lipids in patients with moderate hypercholesterolaemia. Brit. J. Nutr. 86:233–239.
83. Voutilainen, S., Nurmi, T., Mursu, J., and Rissanen, T. H., (2006). Carotenoids and cardiovascular health. Am. J. Clin. Nutr. 83:1265–1271.
84. Weststrate, J. A., van het Hof, K. H., van den Berg, H., Velthuis-Te-Wierik, E. J. M., de Graaf, C., Zimmermanns, N. J. H., Westerterp, K. R., Westerterp-Plantenga, M. S., and Verboeket-van de Venne, W. P. H., (1998). A comparison of the effect of free access to reduced fat products or their full fat equivalents on food intake, body weight, blood lipids and fat-soluble antioxidants levels and haemostasis variables. Eur. J. Clin. Nutr. 52:389–395.
85. Yonekura, L., and Nagao, A., (2007). Intestinal absorption of dietary carotenoids. Mol. Nutr. Food Res. 51:107–115.