PLANT STEROLS IN CHOLESTEROL LOWERING

7 9 of the total proportion of plant sterols in diet Piironen Lampi 2004. The structure of cholesterol and certain unstaturated of plant sterols showed in Figure 3. Figure 3. Chemical structures of cholesterol and plant sterols fitosterol sitosterol, campesterol, dan stigmasterol Plant sterols present in varying amounts in different kinds of plant based food with the highest plant sterols content found in vegetable oils and cereals Piironen et al. 2000. Plant sterols concentrations lower than 100 mg100 g found in oil fraction of coconut, palm, olive, and avocado, while moderate concentrations 100-200 mg100 g were found in peanut oil, soy, hemp, and sunflower seed. Sesame, canola, and corn oil contain plant sterols in higher concentration, between 200-400 mg100 g Phillips et al. 2002. While crude vegetable oils contain the highest amount of plant sterols, the refining process leads to somewhat lower plant sterols levels Piironen Lampi 2004. In cereals, plant sterols are highly localized within the kernel, while the highest amount is contained in germ and bran Piironen Lampi 2004. Piironen and Lampi further explained that the cereal derived products, plant sterols content also depend primarily on vegetable oils and other ingredients added. Meanwhile, fruits and vegetables contain plant sterols in lower levels than the other groups less than 200 mgkg fresh weight, which might be due to their higher water content. Nevertheless, Normen et al. 1999 stated that the role of food in total plant sterols intake depends on the dietary pattern and the way they consumed, which food with small amounts of plant sterols can also significantly contribute to the total intake if consumed in large quantities.

D. PLANT STEROLS IN CHOLESTEROL LOWERING

The utilization of plant sterols as cholesterol-lowering agent has been started since the 1950s Klingberg 2012. Richelle et al. 2004 studied that a low-fat milk based beverage supplemented with 2.2 g plant sterol equivalents provided as either free sterols or sterol esters could decrease cholesterol absorption by 60 when consumed for three weeks. Jones et al. 2000 also stated that consumption of plant sterols of 1.5-1.8 gday could reduce cholesterol absorption by 30- 50. Meanwhile, Hendriks 1999 stated that consumption of plant sterols of 200-400 mgday can keep the blood cholesterol in desirable levels. Although plant sterols present in sufficient quantities in some specific foods, the significance of plant sterols consumption on health depends highly on the diet or consumption pattern Piironen Lampi 2004. Foods with low of plant sterols yet consumed frequently can be a significant, and vice versa. 8 Plant sterols can lower blood cholesterol levels by interfering the absorption of cholesterol through two proposed mechanisms. The first mechanism is related to cholesterol absorption by micelles. In order to be absorbed, cholesterol must attaches to the bile salt micelles to be taken into the blood stream. The presence of plant sterols simultaneously in the small intestine will compete with cholesterol and reduce the incorporation of cholesterol into micelles. Thus, cholesterol did not bind to the micelles will then be passed to the large intestine and excreted via the feces Ikeda Sugano 1983; Hendriks 1999. Plant sterols itself after binding to the micelle can only be absorbed between 0.5 to 10 as it secreted into the small intestine faster than cholesterol Normen, Frohlich, Trautwein 2004. The main type of plant sterols, sitosterol, is much less well absorbed than cholesterol 5 vs 20-60 Clifton 2002. See Figure 4 for illustration of plant sterols mechanism in reducing cholesterol absorption. The second mechanism is the mixture of plant sterols and cholesterol can reduce the cholesterol solubility. The mixture then precipitates and excreted through feces Hendriks 1999. i ii Figure 4. Plant sterols in lowering cholesterol absorption; i cholesterol red circles absorption without presence of plant sterols, ii Cholesterol absorption with presence of plant sterols green circles. Blue circles resembles micelle. http:eurheartj.oxfordjournals.org Several studies proved that the reducing of total and LDL cholesterol can be obtained from the addition of 1.5-2 grams of plant sterols in daily consumption Peterson 1951; Law 2000; Awad Fink 2000. Based on his research, Clifton et al. 2004 also reported that the addition of 2.6 grams of plant sterols esters per day in appropriate type of food can reduce total blood cholesterol and LDL cholesterol levels significantly. The addition of plant sterols to the milk, consumed for 21 days, reduces total blood cholesterol levels by 8.7 and LDL cholesterol by 15.9, and the addition of plant sterols in breads reduces 6.5 and 5.4, respectively. Other studies claimed that people with hypercholesterolemia consuming milk enriched by 2 grams plant sterols per day can decrease total blood cholesterol by 9.62 and LDL cholesterol by 12.2 Jones 2000 in Goncalves et al. 2006. The reduction in LDL cholesterol is dose dependent; a measurable reduction of 6 with an intake of 0.9 gd, 9.6 with an intake of 2 gd, and maximum at 11 with an intake of 3 gd Hendriks 1999; Richelle et al. 2004; Demonty et al. 2009. However, most of the results indicated that 2 gd is nearly as effective and probably represents a more reasonable and achievable dose plant sterols in 9 cholesterol lowering. Consequently, the US National Cholesterol Education Program recommends a plant sterols dose of 2 gd to enhance lowering of LDL cholesterol Carr et al. 2010. Taken together, almost all the findings suggest that intake of plant sterols at levels found naturally in the food supply may exert a minimal cholesterol-lowering effect, but that supplemental doses of plant sterols are required to achieve maximal reductions in serum cholesterol Carr 2010. According to several studies, the reduction of cholesterol by plant sterols generally not depends on the types or classes of plant sterols, since no clear difference has been shown between the different classes of dietary spreads when consumed in identical doses. Both free and saturated plant sterols and their ester derivatives appeared to be equally effective as cholesterol-lowering agents Jones 1999; Law 2000; Clifton 2002. However, efficacy of plant sterols on health, either consumed in natural food or in supplemental form, might depends on several other factors which shown in Table 3. Table 3. Several factors which might influence plant sterols efficacy Possible Factors Suggestion Plant sterols dose - 200-400 mgday from dietary intake can maintain the blood cholesterol in healthy level Hendriks 1999 - 800-1000 mgday from dietary intake can have visible reduction to LDL cholesterol level of 5 or more Berger et al. 2004 - 2 gd to enhance lowering of optimal LDL cholesterol of 9-10 NCEP in Carr et al. 2010 Time of dose Plant sterols should be consumed at each cholesterol containing meal and distributed in 2-3 meals per day to achieve optimal effect Katan et al. 2003; Berger et al. 2004 although more trials are still required. Food vehicle Several studies lead to conclusion that neither the fat content nor the nature of the food as dairy or nondairy significantly affected the LDL cholesterol lowering efficacy of the plant sterols product Carr et al. 2010. However, Berger et al. 2004 reviewed that plant sterols are efficacious when consumed in oil:water emulsion, yogurt, low fat milk, cereal, breads, beverages, and hamburger. Food matrix Plant sterols delivered within solid matrices might be slightly more effective than within liquid foods Demonty et al. 2009 although more trials are still required. Food processing Plant sterols in oils were relatively stable at moderate temperatures, and considerable accumulation of oxides occurred only at high temperatures 140 °C. Food in boiled or steamed form also has no significantly different in plant sterols content compared to the raw form Piironen Lampi 2004 in Dutta 2004. However, milling process in cereals could reduce plant sterols content due to the large amount of sterols in cereals is contained in germ and bran. Combination with other cholesterol- lowering treatments For achieving maximum LDL cholesterol target goals, along with diet and plant sterols alone, certain combination treatments such as statin, bile acid resins cholestyramine, and omega-3 fatty acid, may offer some advantages Carr et al. 2010. The safety and tolerability of plant sterols was determined in an 8-week study in 48 free-living men and women consuming plant sterols up to 9 gd Davidson et al. 2001 in Carr et al. 2010. No adverse effects were observed in several body systems, including musculoskeletal system, skin and appendages, central and peripheral nervous system, gastrointestinal system, extracardiac vascular, and respiratory system, and also there were no psychiatric effects. However, plant sterol in supplemental doses is not recommended for normocholesterolemic children under five years old because they have a large need for cholesterol for normal development Berger et al. 2004. 10

E. EARLIER STUDIES ON PLANT STEROLS INTAKE