Reduction of Cholesterol by Alternative Therapies

Cholesterol- & Glucose-lowering Functional Foods

Red Yeast Rice

Red yeast rice is the product of fermentation of rice by red yeast (Monascus purpureus) and is served as a dietary staple in some Asian countries. It contains several compounds collectively known as monacolins, substances known to inhibit HMG-CoA reductase (the rate-limiting enzyme in cholesterol biosynthesis) and is also known as mevinolin or lovastatin (Mevacor®; Merck & Co., Inc., NJ, USA). Several clinical trials conducted in China as well as other countries have reported that red yeast rice or its extracts (Xuezhikang) exert hypolipidemic effects. In this regard, decreases in total cholesterol, LDL-C and TG levels, and an increase in HDL-C have been reported in patients with coronary heart disease (CHD) following treatment with red yeast rice extracts.^[11,12] The effects of several nutraceutical formulations containing red yeast rice have also been studied in patients with dyslipidemia. Marazzi et al. reported that a pill composed of 200 mg red yeast rice, 0.2 mg folic acid, 2 mg coenzyme Q10 and 0.5 mg astaxanthin reduced total cholesterol (20%), LDL-C (31%) and insulin resistance (10%) in 106 dyslipidemic patients after a 12-month treatment.^[13]

Lee et al. have reported that a combination of red yeast rice, bitter gourd, chlorella, soy protein and licorice extracts significantly decreased total cholesterol, LDL-C and TG levels in patients with metabolic syndrome following a 12-week treatment period.^[14] Some beverages containing red yeast rice have also been studied in multicenter clinical trials in patients with dyslipidemia. Karl et al. observed that a beverage containing red yeast rice significantly reduced total cholesterol (14%) and LDL-C (17%) after an 8-week treatment in 59 subjects with dyslipidemia.^[15] In a double-blind, randomized, parallel-controlled clinical trial, a beverage containing red yeast rice, sugar cane-derived policosanols and artichoke leaf reduced the levels of total cholesterol (14%) and LDL-C (21%) in 39 patients with moderate hypercholesterolemia.^[16] Thus, from these studies, it appears that red yeast rice is able to lower total cholesterol and LDL-C levels in patients with abnormal lipid profiles. The safety of red yeast rice products have not yet been established; however, some supplements have been found to contain high levels of the toxin citrinin, as well as varying amounts of monacolins^[17] and thus the possible risks are associated with those of statins.^[3,4]

Goji Berry

Goji berry or Wolfberry is the fruit of Lycium barbarum. As a food, dried wolfberries are traditionally cooked before consumption. The dry berry has also been used for the treatment of diabetes by practitioners of traditional Chinese medicine. It contains polysaccharides, carotene, ascorbic acid, betaine and zeaxanthin;^[18] these components of goji berry have been observed to exhibit antioxidant properties. Recently, it has been found that goji berry juice and other extracts have beneficial effects in diabetic animals. Amagase et al. have reported that goji berry extracts have antioxidant effects in humans.^[19] In this double-blinded, placebo-controlled clinical trial, 50 healthy adults between the ages of 55 and 72 years received 120 ml/day goji juice for 30 days. It was observed that levels of malondialdehyde (a lipid peroxide product and marker of oxidative stress) were significantly decreased, while the activities of the endogenous antioxidant enzymes, superoxide dismutase and glutathione peroxidase, were significantly increased.

In another clinical trial conducted by Bucheli et al. involving 150 healthy elderly volunteers, 75 participants received 13.7 g/day of goji berry for 90 days and the remainder received placebo.^[20] It was found that serum zeaxanthin (a carotenoid) and total antioxidant capacity were significantly increased by the goji berry treatment. The authors concluded that dietary supplementation of goji berry for 30–90 days may prevent or reduce free radical-induced cell damage. The antidiabetic effect of goji berry has also been reported in animal studies.^[21] The three preparations of goji berry (water decoction, crude polysaccharide and purified polysaccharide fractions) were tested in alloxan-induced diabetic rabbits. All these preparations of goji berry improved glucose tolerance, as well as reduced LDL-C and TG levels, while an increase in HDL-C concentration was observed. In addition, these goji berry preparations also exerted antioxidant effects to varying degrees of potency. With respect to safety, two case reports have described elderly women who experienced increased bleeding after drinking high quantities of wolfberry tea.^[22,23] In addition, there is a potential interaction between warfarin and undefined wolfberry phytochemicals.^[22] Atropine, a toxic alkaloid, is found in the wolfberry fruit.^[24] Adverse reactions to atropine include myocardial abnormalities such as ventricular fibrillation and ventricular tachycardia, as well as dizziness and nausea. Thus, excessive consumption must be cautioned.

Indian Gooseberry

Emblica officinalis Gaertn., commonly known as the Indian gooseberry or 'Amla', has been used as health food for centuries in India and other Asian countries. The biological effects of Amla have been attributed to the antioxidant properties of low-molecular-weight hydrolysable tannins present in the fruit. Amlamax™ is a purified, standardized, dried extract of Amla containing approximately 35% galloellagi tannins in addition to other hydrolysable tannins.^[25] Animal studies have reported the prevention of age-related hyperlipidemia through attenuation of oxidative stress in the aging process in the rat.^[26] The effects of daily consumption of two different doses (500 and 1000 mg) for 6 months have been evaluated in normal healthy volunteers.^[26] Total and LDL-Cs were decreased, whereas increases in HDL-C levels were observed. In addition, a reduction in the levels of CRP, an inflammatory marker, was also observed. Since dyslipidemia and inflammation are the two major components of CVD, these findings indicate the potential of Amlamax in the prevention/reduction in risk for CVD.

In one of the earliest trials on Amla, examining serum cholesterol levels in hypercholesterolemic men aged 35–55 years,^[27] it was demonstrated that a 4-week daily dietary supplementation with raw Amla resulted in a reduction in total cholesterol levels. Furthermore, the cholesterol levels reverted back to baseline values after withdrawal of the Amla supplement. The antihyperglycemic and lipid-lowering properties of E. officinalis Gaertn. fruit in diabetic subjects have been recently reported.^[28] A significant decrease in fasting and postprandial blood glucose levels in diabetics was observed on the 21st day of the supplementation. Decreases in total cholesterol and TGs were also observed in the diabetic patients. In fact, E. officinalis Gaertn. significantly improved HDL-C levels and decreased LDL-C levels. It is interesting to note that the hypolipidemic effects of an Ayurvedic herbal formulation, Triphala (Terminalia chebula, Terminalia belerica and E. officinalis) have been demonstrated in hypercholesterolemic rats.^[29] Moreover, a 45-day supplementation with Triphala powder has been reported to significantly reduce blood glucose levels in patients with Type 2 diabetes.^[30] Although experimental studies have demonstrated hypolipidemic or hypoglycemic effects of Terminalia chebula and Terminalia belerica on their own,^[31–34] clinical trials are needed in order to further understand the individual therapeutic potential of these indigenous drugs. Indian gooseberry seems safe for most people when consumed in the amounts found in foods. However, to date, there is a lack of information regarding its safety in medicinal amounts, which are much larger.

Artichoke

Artichoke (Cynara cardunculus var. scolymus) is a cultivated variety of a species of thistle and is cultivated as a food. The hypocholesterolemic effects of artichoke have been reported in the literature.^[35–37] The efficacy and tolerability of artichoke dry extract as coated tablets containing 450 mg extract has also been investigated in the treatment of hyperlipoproteinemia.^[35] In this double-blinded, placebo-controlled trial, 143 adult patients with initial total cholesterol of >7.3 mmol/l (>280 mg/dl) were randomized to receive 1800 mg artichoke dry extract per day or placebo for 6 weeks. Decreases in the total cholesterol (by 19%) and LDL-C (by 23%) in the artichoke group were observed. The LDL:HDL ratio was also decreased (by 20%) in the treated group. It was suggested that artichoke dry extract could be of therapeutic value for treating hyperlipoproteinemia and prevention of atherosclerosis and CHD.^[35] In another study, conducted in 75 hypercholesterolemic adults with baseline values for total plasma cholesterol in the range of 6.0–8.0 mmol/l,^[36] a 12-week daily intervention with artichoke leaf extract resulted in a reduction of the total cholesterol by an average of 4% (from 7.16 mmol/l [standard deviation: 0.62] to 6.86 mmol/l (standard deviation: 0.68]).

Although some limited data from rigorous clinical trials assessing artichoke leaf extract for the treatment of hypercholesterolemia exist, beneficial effects are reported; however, larger clinical trials are warranted. It is interesting to note that in a double-blinded study conducted in high-intensity athletes,^[37] 400 mg of artichoke-leaf extract three times a day for 5 weeks resulted in a decrease in serum total cholesterol levels. Furthermore, a higher plasma total antioxidant capacity, as evidenced by measuring red blood cell superoxide dismutase, glutathione peroxidise and glutathione reductase activities, as well as reduced glutathione and thiobarbituric acid reactive substances levels, was observed, but did not limit oxidative damage to erythrocytes.

Rhubarb

Rhubarb (Rheum rhapontiam) is usually considered to be a vegetable, but in the USA, it is considered as a fruit. Preclinical studies with rhubarb stalk fiber in streptozotocin-induced diabetic rats and diabetes-prone BB rats have reported a lack of cholesterol-lowering action of dietary rhubarb stalk fiber.^[38] However, a cholesterol-lowering effect in hypercholesterolemic men has been reported.^[39] In this study, ten hypercholesterolemic men were given 27 g/day of ground rhubarb stalk fiber for 4 weeks. Rhubarb fiber supplementation resulted in significant lowering of serum total cholesterol (8%) and LDL-C (9%), while HDL-C concentrations remained unchanged. The depressed total and LDL-C levels returned to baseline after the fiber supplementation was withdrawn for 1 month. It was claimed that rhubarb stalk fiber is effective in lowering serum cholesterol concentrations, especially LDL-C, in hypercholesterolemic men. These results signify the potential use of underutilized rhubarb crop; however, further clinical trials are required. Although rhubarb leaves contain oxalic acid, which is a nephrotoxic,^[40] very low amounts are seen in the raw stalks^[41] and thus may not be a safety concern.