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Tracy Beckmann May 21, 2012 Are There Adverse Effects in Adults Who Consume Plant Sterols and Stanols? Cardiovascular disease (CVD) is the number one cause of death in the United States.1 The first line of treatment includes medical nutrition therapy focusing on evidence-based diet and lifestyle changes that reduce the risk factors for developing CVD. One such method addresses atherosclerosis with the goal of lowering LDL cholesterol levels, which are known to contribute to plaque build-up in the arteries.2 Plant sterols and stanols have been studied primarily for their LDL lowering ability since the 1950s3 and are currently used as ingredients in functional food products such as margarine, butter, bread, and cereal.4 This paper evaluates the safety of plant sterols and stanols to determine if there are any adverse effects to adults who consume such foods. Background Plant (or phyto) sterols and stanols can be thought of as “plant cholesterol”; they are naturallyoccurring saturated compounds that provide plant membrane structure and, in that respect, have a similar configuration to animal cholesterol.5 Phytosterols are obtained by humans solely in the diet and contain both sterols and stanols, with stanols comprising a small amount (only about 10%) of daily phytosterol intake.5 It is estimated that the typical Western diet contains approximately 200-500 mg cholesterol, 200-400 mg phytosterols and 50 mg phytostanols,6 with the plant compounds obtained from fruits, vegetables, and functional foods. When eaten, phytosterols compete with cholesterol (dietary and endogenous) for micelle uptake in the human intestine.7 Because phytosterols are absorbed at a much lower rate than cholesterol (about 10% as compared to 50-60%, respectively), they are present in lower concentrations in the blood, are 1 excreted more rapidly, and result in decreased LDL transport.5, 7 These results have been seen in numerous studies involving diverse human subjects including males and females of varying adult ages and disease conditions, although all had been diagnosed with hyperlipidemia.3-8 Recommendations Phytosterols have been deemed Generally Recognized as Safe (GRAS) by the United States Food and Drug Administration.9 Several countries, including Europe, Australia, and the United States recommend intakes of these plant compounds at 2 g/day by adults with and at risk for hyperlipidemia and CVD.8, 10-11 This amount, almost exclusively obtained via functional foods, has been shown effective in reducing LDL cholesterol absorption by roughly 10%.12-13 Intakes of greater than 2-3 g/day are not currently advised as research showing more substantial LDL reductions with greater intake is lacking.6, 8, 11-13 The current guidelines are based on human studies averaging 1 year in length; longer-term studies have not been conducted in significant numbers of subjects.8 Adverse Effects Phytosterols are not advised for the general population as adverse effects have been seen in individuals with homozygous sitosterolemia (phytosterolemia), a rare hereditary condition that allows increased phytosterol absorption with decreased biliary excretion and results in high plasma phytosterol levels.8, 14 As noted above, phytosterols are typically low in human plasma; at elevated levels there is an increased incidence of premature atherosclerosis.8, 14 Additionally, phytosterols are not advised for pregnant or breastfeeding women due to insufficient research15 although no contrary evidence has been documented among vegetarian or vegan women (populations with increased phytosterol intakes due to diet) who were pregnant or lactating.14 2 Among people at high risk for hyperlipidemia and CVD who follow the current phytosterol guidelines, some individuals may experience nausea, constipation, diarrhea, or indigestion.14-15 The most serious adverse effect seen in this population is decreased plasma carotenoid levels, especially beta carotene.6-8, 11-15 This phytosterol-induced nutrient deficiency has been associated with increased incidences of type 2 diabetes and other metabolic disturbances.8, 15 However, this can be remedied by incorporating one additional carotenoid-rich fruit or vegetable (beyond the recommended five) into the diet each day.16 Conclusion Individuals facing increased risk for CVD, including hyperlipidemia, have several therapeutic options directed towards diet and lifestyle change aimed to lower their risk. Among these options are increased plant sterol and stanol intake by means of fat-derived functional food products. After reviewing the literature and current recommendations, it is my finding that the incorporation of plant sterols and stanols at amounts of 2 g/day, but not more than 3 g/day, may safely result in decreased LDL cholesterol levels. I would recommend the inclusion of dietary phytosterols to my clients with high LDL levels for whom initial diet and lifestyle changes did not achieve desired results. Additionally, I’d impress the need for them to consume six or more servings of fruits and vegetables each day, with at least 2 of those servings containing beta carotene-rich foods such as carrots, collards, and kale. 3 References: 1. Heart Disease Facts. Centers for Disease Control and Prevention web site. Updated March 2012. http://www.cdc.gov/heartdisease/facts.htm Accessed May 15, 2012. 2. Escott-Stump S. Cardiovascular Disorders. In: Nutrition and Diagnosis-Related Care, 7th Ed. Baltimore, MD: Lippincott Williams & Wilkins; 2012:336-343. 3. Pollak OJ. Reduction of blood cholesterol in man. Circulation. 1953;2:702–706. http://circ.ahajournals.org/content/7/5/702.full.pdf+html Accessed May 15, 2012. 4. Nestel P, Cehun M, Pomeroy S, Abbey M, Weldon G. Cholesterol-lowering effects of plant sterol esters and non-esterified stanols in margarine, butter and low-fat foods. European Journal of Clinical Nutrition. 2001:55;1084–1090. www.nature.com/ejcn Accessed on May 15, 2012. 5. Sudhop T, Lqtjohann D, von Bergmann K. Sterol transporters: targets of natural sterols and new lipid lowering drugs. Pharmacology & Therapeutics. 2005:105; 333–341. http://oregonstate.summon.serialssolutions.com/search/results?q=Sterol+transporters%3A+target s+of+natural+sterols+and+new+lipid+lowering+drugs&x=0&y=0 Accessed May 15, 2012. 6. Weingartner O, Bohm M, Laufs U. Controversial role of plant sterol esters in the management of hypercholesterolaemia. European Heart Journal. 2009:30;404–409. doi:10.1093/eurheartj/ehn580. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2642922/ Accessed May 15, 2012. 7. Ellegard LH, Andersson SW, Norme’n LA, Andersson HA. Dietary Plant Sterols and Cholesterol Metabolism. Nutrition Reviews. 2007: 65:1;39–45. http://onlinelibrary.wiley.com.proxy.library.oregonstate.edu/doi/10.1111/j.17534887.2007.tb00266.x/pdf Accessed May 15, 2012. 8. Summary of Evidence. Phytosterol/Stanol enriched foods. Heart Foundation of Austrailia. Updated 2009. http://www.heartfoundation.org.au/SiteCollectionDocuments/HW-FS-SterolStanols-SummEv-Update2009.pdf Accessed May 15, 2012. 9. Plant Stanols and Sterols. U.S. Food and Drug Adminstration website. http://www.accessdata.fda.gov/scripts/fcn/gras_notices/grn000177.pdf?utm_campaign=Google2 &utm_source=fdaSearch&utm_medium=website&utm_term=gras%20sterol&utm_content=1 Accessed on May 15, 2012. 10. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). U.S. Department of Health and Human Services. National Cholesterol Education Program website. Updated 2004. http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm Accessed May 15, 2012. 4 11. Plant Stanol Esters and Blood Cholesterol. European Food Safety Authority Journal. 2008:825;10-13. http://www.efsa.europa.eu/fr/scdocs/doc/825.pdf Accessed May 15,2012. 12. Katan MB, Grundy SM, Jones P, Law M, Miettinen T, Paoletti R. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc.2003;78(8):965-78. http://www.ncbi.nlm.nih.gov/pubmed/12911045 Accessed May 15, 2012. 13. Clifton PM, Noakes M, Ross D, Fassoulakis A, Cebun M, Nestel P. High dietary intake of phytosterol esters decreases carotenoids and increases plasma plant sterol levels with no additional cholesterol lowering. Journal of Lipid Research. 2004:45;1493-1499. DOI 10.1194/jlr.M400074-JLR20. http://www.jlr.org/content/45/8/1493 Accessed May 15, 2012. 14. Micronutrient Information Center: Phytosterols. Linus Pauling Institute. Oregon State University. Updated 2008. http://lpi.oregonstate.edu/infocenter/phytochemicals/sterols/ Accessed May 15, 2012. 15. Carr TP, Ash MM, Brown AW. Cholesterol-lowering phytosterols: factors affecting their use and efficacy. Nutrition and Dietary Supplements. 2010:2 59–72. http://www.dovepress.com/cholesterol-lowering-phytosterols-factors-affecting-their-use-andeffi-peer-reviewed-article-NDS-recommendation1 Accessed May 15, 2012. 16. Noakes M, Clifton P, Ntanios F, Shrapnel W, Record I, McInerney J. An increase in dietary carotenoids when consuming plant sterols or stanols is effective in maintaining plasma carotenoid concentrations. Am J Clin Nutr 2002;75:79-86. http://www.ncbi.nlm.nih.gov/pubmed/117560635 Accessed May 15, 2012. 5