**5. Dietary supplement**

314 Lipoproteins – Role in Health and Diseases

to include all individuals [191].

**4.7. Dietary pattern** 

relation between egg consumption and risk of coronary heart disease [187,188], may be because dietary cholesterol increases not only concentrations of total and LDL cholesterol but also concentrations of HDL cholesterol [21,186,189,190]. Egg intake has been also shown to promote the formation of large LDL particles, which is less atherogenic [191]. Therefore dietary recommendations aimed at restricting egg consumption should not be generalized

Using single nutrients or dietary food groups have some limitations in assessing their effect on lipid profiles separately because nutrients and foods are consumed in combination. To date, dietary patterns consider how foods are consumed in combination, and are used to evaluate the effects of overall nutritional habits on health status. There are two dietary patterns that demonstrate the beneficial effect on disturbances of lipoprotein concentrations; there include the dietary to stop hypertension (DASH) and the Mediterranean diet. The DASH dietary pattern, rich in fruits, vegetables, and low-fat dairy foods, emphasizes fish, poultry, and whole grains, and is reduced in total fat, SFAs and cholesterol, red meat, sweets, and sweetened beverages [192,193]; it lowers total, LDL and HDL cholesterols, without any adverse effects on triglyceride concentrations [194]; all of these coupled with decrease in blood pressure, reduce 10-year coronary heart disease risk of approximately 12% [194]. The Mediterranean dietary pattern consists of: (a) daily consumption: of non refined cereals and products (whole grain bread, pasta, brown rice, etc), vegetables (2 – 3 servings/ day), fruits (6 servings/day), olive oil (as the main added lipid) and dairy products (1 – 2 servings/day), (b) weekly consumption: of fish (4–5 servings/week), poultry (3 – 4 servings/week), olives, pulses, and nuts (3 servings/ week), potatoes, eggs and sweets (3 – 4 servings/week) and monthly consumption: of red meat and meat products (4 – 5 servings/month). It is also characterized by moderate consumption of wine (1 – 2 wineglasses/day). Mediterranean diet is a diet poor in SFAs and PUFAs but rich in MUFA (oleic acid) provided by the olive oil. The ratio of MUFAs : SFAs fat ratio is high > 2 [195]. This diet pattern is associated with reduction in total and LDL-cholesterol, and also a significant effect on triglycerides and VLDL concentrations, and a small positive or no effect on HDL-cholesterol [196-199] and improves dyslipidemia in dislipidemic patients [200]. This diet also includes antioxidant vitamins and phenolic compounds, and therefore reduces levels of circulating oxidized LDL and increases total antioxidant capacity [201]. Beside these two dietary patterns, other dietary pattern such as the western, and healthy dietary patterns affect lipoprotein profiles. The western pattern is characterized by high consumption of food such as refined grains, french fries, and red meats that have detrimental effects on lipid profiles. The healthy pattern included non-hydrogenated fat, vegetables, eggs, and fish and was negatively associated with lipoprotein disturbances [202-205]. In addition of dietary patterns, therapeutic lifestyle change is another dietary approach that ATP III recommends to reduce risks for CHD. This dietary approach includes the following: 1) Reduced intakes of dietary SFAs (<7% of total calories) and cholesterol (<200 mg/d), 2) weight reduction, 3) increased physical activity, and 4) therapeutic options for enhancing LDL lowering such as

plant stanols/ sterols (2 g/d) and increased viscous (soluble) fiber (10-25 g/d) [18].

#### **5.1. Plant stanols and sterols**

Dyslipidemia may be treated with dietary interventions, including the daily consumption of foods with added plant stanols or plant sterols. Plant sterols are isolated from soybean and tall pine-tree oils. Also some foods such as macadamia nuts are a rich source (1.28 mg/g lipid) of plant sterols. Plant sterols can be esterified to unsaturated fatty acids, creating sterol esters, to increase lipid solubility. Hydrogenating of sterols produces plant stanols. Plant stanols and sterols are available in commercial margarines. Daily consumption of 2 g plant stanols or plant sterols, expressed as free plant stanol or plant sterol equivalents improves dyslipidemia [18]. FDA confirms a daily dose of plant sterols and stanols of 2 g per day as safe, a dose which reduces LDL cholesterol by 10% [206], with little or no change in HDL cholesterol or triglyceride levels. There were no apparent added benefits at higher doses of palnts stanols and sterols. Plant stanols and sterols compete with absorption of dietary cholesterol and bile acid [8]. The consumption of plant stanols and sterols is an effective LDL cholesterol lowering strategy for patients who are undergoing statin therapy. The lipidlowering response to combined plant stanols and sterols/statin therapy target both intestinal and hepatic cholesterol metabolism. Consumption of plant stanols and sterols reduces intestinal cholesterol absorption and reduces hepatic cholesterol synthesis. Consumption of statins simultaneously with plant stanols and sterols inhibit hepatic cholesterol synthesis and therefore reduce in LDL cholesterol concentrations [8]. Plant sterols/stanols reduce absorption of dietary carotenoids, and decrease levels of plasma betacarotene**;** therefore increased intakes of fruits and vegetables are recommended with consumption of plant stanols/sterols[18].

### **5.2. Herbal**

There is a need to identify additional non-pharmacologic therapeutic options for cholesterol lowering. There is also a need to find products that are more practical for the consumer than viscous fiber and plant stanols and sterols to permit widespread adoption.

#### *5.2.1. Flavonoid*

Flavonoids have 2 aromatic rings that are bound by an oxygenated heterocyclic ring. On the basis of their chemical structure, they are divided into several subclasses: flavones, flavonols, flavanones, flavan-3-ols, anthocyanins and isoflavones. Flavones and flavonols are found in leaf vegetables and onion. Flavanones are mainly found in grapefruits and citrus fruits. Tea and cocoa are the richest sources of flavan-3-ols. Soy and soy products such as tofu, and miso are the main sources of isoflavones [207,208]. Although increased resistance of LDL to oxidation was observed after treatment with various synthetic pharmaceutical agents, an effort is made to identify natural food products which can offer antioxidant defense against LDL oxidation. Polyphenolic flavonoids are powerful antioxidants and their antioxidative capacity is related to their chemical structure [209].

Incubation of LDL with flavonoids protects the lipoprotein against oxidation [210]. Certain flavonoids such as querectin could have a potentially protective role in suppression of LDL oxidation, regardless of the effect of antioxidant vitamins [211] via scavenging radicals and reduce total and LDL cholesterol concentrations, by reducing the hepatic lipogenesis [212].

#### *5.2.2. Tea*

The effect of tea on lipid profiles is uncertain. Although some studies have found no lipidlowering effects from green or black tea consumption, most showed hypolipidemic effects for tea [213-218]. The association between tea drinking and lipid profile concentrations was linear for up to 10 cups per day, beyond which the association disappeared [219]. Daily consumption of 10 cups of green tea was associated with a reduction of approximately 2% in serum total cholesterol [219]. Tea also is a major source of flavonoids, the predominant ones in green tea being catechins. Theaflavins are polyphenol pigments present in black tea, formed from the polymerization of catechins during fermentation of green tea [220]. Catechins reduce intestinal cholesterol absorption [221], reduce hepatic cholesterol content [222] and increase fecal excretion of total fatty acids, neutral sterols, and acidic sterols [223] and up-regulate the LDL receptor in liver cells [224]. Polyphenol in black tea also increases fecal excretion of total lipids and cholesterol [225].

#### *5.2.3. Chocolate*

The beneficial effects of chocolate on healthy humans have been widely addressed in recent years. Supplementation of cocoa products affects lipid profiles in subjects with cardiovascular-related diseases such as hypercholesterolemia, glucose intolerance, and hypertension as well as healthy individuals [226-228]. Consumption of cocoa and dark chocolate increase the concentration of HDL cholesterol [229] and plasma antioxidant capacity, decrease the formation of lipid oxidation products, and inhibit the oxidation of LDL [230]. In a meta-analysis study, cocoa was associated with small decreases in total and LDL cholesterol, but not HDL cholesterol concentrations [231]. Cocoa products contain more polyphenols than teas. A particular group of flavonoids, namely, the flavan-3-ols was found in chocolate (flavanols) [232]. Moderate consumption of cocoa or dark chocolate, have potential health benefits [231], however, a high dose of polyphenols has been shown to exert cytotoxic effects on liver cells [233] and higher polyphenol supplementation may counteract its beneficial biological effects on lipid metabolism [234].

#### *5.2.4. Fenugreek*

Fenugreek (Trigonella foenum-graecum), an annual medicinal plant of the Fabaceae family is well documented for its pharmacological properties. Fenugreek seeds have been historically used for the treatment of various chronic diseases such as diabetes, dyslipidemia, and obesity [235,236 ]. The seeds of Fenugreek contain many nutrients including protein, carbohydrates, fat, vitamin, and minerals, fiber, saponins, choline and trigonelline, polyphenolic flavonoids, steroid saponins, polysaccharides mainly galactomannans and 4-hydroxyisoleucine [237,239], the fiber and saponin components of the seeds have been shown to have hypocholesterolemic effect [240], and the beneficial effect of raw fenugreek seeds on elevated serum cholesterol levels has been well established [241]. Raw fenugreek seeds reduce serum total cholesterol, LDL cholesterol, VLDL cholesterol and triglyceride concentrations, without altering the HDL fraction [242]; intakes of 20–25 g in three divided doses yielded maximum benefit in the control of cholesterol concentrations [243]. Its use as a dietary adjunct however is limited because of its bitterness. Soaking and washing of fenugreek seeds in water overnight removes the bitterness to a certain extent and makes then edible [243,244].

#### *5.2.5. Ginseng*

316 Lipoproteins – Role in Health and Diseases

fecal excretion of total lipids and cholesterol [225].

its beneficial biological effects on lipid metabolism [234].

*5.2.2. Tea* 

*5.2.3. Chocolate* 

*5.2.4. Fenugreek* 

Incubation of LDL with flavonoids protects the lipoprotein against oxidation [210]. Certain flavonoids such as querectin could have a potentially protective role in suppression of LDL oxidation, regardless of the effect of antioxidant vitamins [211] via scavenging radicals and reduce total and LDL cholesterol concentrations, by reducing the hepatic lipogenesis [212].

The effect of tea on lipid profiles is uncertain. Although some studies have found no lipidlowering effects from green or black tea consumption, most showed hypolipidemic effects for tea [213-218]. The association between tea drinking and lipid profile concentrations was linear for up to 10 cups per day, beyond which the association disappeared [219]. Daily consumption of 10 cups of green tea was associated with a reduction of approximately 2% in serum total cholesterol [219]. Tea also is a major source of flavonoids, the predominant ones in green tea being catechins. Theaflavins are polyphenol pigments present in black tea, formed from the polymerization of catechins during fermentation of green tea [220]. Catechins reduce intestinal cholesterol absorption [221], reduce hepatic cholesterol content [222] and increase fecal excretion of total fatty acids, neutral sterols, and acidic sterols [223] and up-regulate the LDL receptor in liver cells [224]. Polyphenol in black tea also increases

The beneficial effects of chocolate on healthy humans have been widely addressed in recent years. Supplementation of cocoa products affects lipid profiles in subjects with cardiovascular-related diseases such as hypercholesterolemia, glucose intolerance, and hypertension as well as healthy individuals [226-228]. Consumption of cocoa and dark chocolate increase the concentration of HDL cholesterol [229] and plasma antioxidant capacity, decrease the formation of lipid oxidation products, and inhibit the oxidation of LDL [230]. In a meta-analysis study, cocoa was associated with small decreases in total and LDL cholesterol, but not HDL cholesterol concentrations [231]. Cocoa products contain more polyphenols than teas. A particular group of flavonoids, namely, the flavan-3-ols was found in chocolate (flavanols) [232]. Moderate consumption of cocoa or dark chocolate, have potential health benefits [231], however, a high dose of polyphenols has been shown to exert cytotoxic effects on liver cells [233] and higher polyphenol supplementation may counteract

Fenugreek (Trigonella foenum-graecum), an annual medicinal plant of the Fabaceae family is well documented for its pharmacological properties. Fenugreek seeds have been historically used for the treatment of various chronic diseases such as diabetes, dyslipidemia, and obesity [235,236 ]. The seeds of Fenugreek contain many nutrients including protein, carbohydrates, fat, vitamin, and minerals, fiber, saponins, choline and The beneficial metabolic effects of ginseng on lipid profiles as a hypolipidemic agent were reported over 20 years ago **[**245-247]. Ginseng leads to reduction of cholesterol and triglyceride concentrations in liver and serum. Administration of red ginseng powder and extract reduces plasma total cholesterol, triglycerides, FFA, and increased HDL-C [248,249 ]. Ginseng saponins may decrease blood cholesterol concentrations by increasing cholesterol excretion through bile acid formation [249,250]. Ginsenoside, one of active components of ginseng saponins, may accelerate serum cholesterol turnover by increased cholesterol degradation and excretion in the feaces notwithstanding increased hepatic cholesterogenesis [250,251]. Ginseng saponins as ginsenosides increase LDL receptors by promoting the synthesis of LDL receptors[252].

#### *5.2.6. Ginger*

Ginger has been listed in the ''Generally Recognized as Safe'' by FDA [338]; fresh ginger rhizome contains polyphenolic compounds such as gingerols; zingerone, which is the major active component and gingerol, is one of the most abundant constituents in the gingerol series and also responsible for its characteristic pungent taste [253,254]. Ginger oleo-resin and dried ginger rhizome reduce hypercholesterolaemia. The speculated mechanism for these compounds is by disrupting cholesterol absorption from the gastro-intestinal tract [255], which may be due to the presence of niacin in ginger, and it causes increased clearance of VLDL, lowers triglyceride levels, increases hepatic uptake of LDL and inhibition of cholesterogenesis [256]. Ginger powder significantly reduces the extent of lipid peroxidation and improves plasma antioxidant capacity, which decreases plasma-free radicals [257]. Moreover, polyphenolic flavonoids present in ginger may prevent coronary artery disease by reducing plasma cholesterol levels or by inhibiting LDL oxidation [258]. Reduction in serum triglycerides is dose dependent; doses of 200 and 400 mg/kg of ginger are more effective as antihypercholesterolaemics than atorvastatin when given for 4 weeks and are equivalent to it when given for shorter period under the same conditions of diet and life style for the treatment of the same pathologic condition. The triglyceride lowering effect of ginger may be due to ginger's ability to enhance lipase activity [255].

### *5.2.7. Licorice*

Licorice root, derived from the plant Glycyrrhiza glabra is used widely in Asia as a sweetener or a spice, contains flavonoids from the flavan and chalcone subclasses, and has a antioxidative properties [259]. Licorice-derived glabridin binds to the LDL particle and protects it from oxidation by its capacity to scavenge free radicals and its property to reduce the LDL aggregation [260,261].
