From the August 2002 Issue of Natural Foods Merchandiser
By Ronald P. Mensink, Ph.D., Jogchum Plat, Ph.D.,
and Danielle Ajm Kerckhoffs
A new era of molecular nutrition points to the importance of diet, including the burgeoning array of functional foods, in lowering cholesterol.
Coronary heart disease (CHD) is still the leading cause of morbidity and mortality in the Western world, but its prognosis has improved during the past decades, in part because of better understanding of CHD's underlying pathology. Researchers have identified factors, both modifiable and nonmodifiable, that are associated with CHD risk. Much research on CHD risk has focused specifically on the distribution of cholesterol through different lipoproteins. For example, elevated low-density lipoprotein levels or low high-density lipoprotein levels signal an unfavorable fasting lipoprotein profile. Moreover, evidence is mounting that increased serum triacylglycerol concentration is positively related to cardiovascular risk. 
Diet is a cornerstone for improving unfavorable lipoprotein profiles. Studies continue to support dietary advice that focuses on reducing cholesterol as well as saturated and trans fatty acid intake; eating more vegetables, fruits and whole grains; and preventing obesity. [2, 3] By achieving these goals, people can often reduce their LDL cholesterol by 10 percent to 15 percent.
Functional foods offer further lipid profile improvements. Most promising are soy protein, soluble fiber, fish oils and plant sterols or stanols, all of which help improve serum lipoprotein profiles.
The U.S. Food and Drug Administration has approved a health claim that 25 g soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce heart disease risk.  Several dietary intervention trials have shown that when soy consumption increases, serum lipoprotein profiles improve. The precise mechanism for this effect is unknown, but researchers have suggested several possible explanations, including a higher bile acid excretion or an enhanced LDL receptor activity. 
A meta-analysis published in The New England Journal of Medicine in 1995 estimated that an average daily intake of 47 g soy protein, instead of animal protein, lowered serum total and LDL cholesterol concentrations by 9 percent and 13 percent respectively, and triacylglycerol by 11 percent.  HDL cholesterol was not affected. Researchers found subjects with high cholesterol levels more responsive than those with mildly elevated levels.
In fact, most individual studies involving soy-containing products and subjects with normal or slightly increased total cholesterol levels did not demonstrate a significant serum lipoprotein profile improvement. Therefore, it remains to be resolved whether soy-containing products are only beneficial for significantly hyperlipidemic subjects. Further, it remains to be determined whether benefits are the result of soy protein per se or of soy's isoflavones. In the aforementioned meta-analysis, the researchers could not demonstrate a difference in effect between isolated soy protein and textured soy protein. In other studies examined in the meta-analysis, however, researchers have suggested that soy's isoflavones account for up to 60 percent of soy's cholesterol-lowering effects. 
The effects of isolated isoflavones on serum LDL cholesterol concentrations in hypercholesterolemic subjects are inconsistent. In one randomized, controlled clinical trial involving 156 healthy men and women, researchers found a significant reduction in serum LDL cholesterol concentrations when subjects ate soy protein with isoflavones compared with soy protein depleted of isoflavones.  Further, essentially the same findings were described in hypercholesterolemic postmenopausal women.  In contrast, a third trial with a similar approach did not confirm these findings. In fact, both the isoflavone-rich and isoflavone-poor soy proteins significantly improved the serum lipoprotein profile when compared with protein from casein and nonfat dry milk.  Also, 80 mg isoflavones in supplement form did not induce significant cholesterol lowering in menopausal and perimenopausal women with normal cholesterol levels.  However, systemic arterial flexibility was significantly improved.
These conflicting findings do not strongly support the notion that it is just the isoflavones responsible for the potential cholesterol lowering effect of soy-containing products. It is possible, however, that isoflavones are only effective in combination with other components from soy, such as proteins or saponins.
Dietary fibers, which are resistant to digestion by enzymes in the gastrointestinal tract, can be divided into water-soluble and insoluble fibers. The water-soluble (or viscous) fibers have long been recognized for their ability to lower serum cholesterol concentrations. The effective fiber from oats is beta-glucan.  In 1997, the FDA approved the health claim that "a diet high in soluble fiber from whole oats and low in saturated fat and cholesterol may reduce the risk of heart disease." 
To achieve a clinically relevant reduction in total serum cholesterol concentrations, a person has to eat at least 3 g beta-glucan per day from oats. Based on a meta-analysis, researchers estimated that such an amount of soluble fibers from oats lowered serum cholesterol concentrations an average of 0.13 mmol/L (5 mg/dL) in subjects with a serum cholesterol concentration below 5.9 mmol/L (227 mg/dL) and by 0.41 mmol/L (16 mg/dL) in hypercholesterolemic subjects.  In general, researchers did not observe an effect on HDL cholesterol or triacylglycerol concentrations. LDL cholesterol reductions were found to be dose-dependent. [13, 14]
Researchers have proposed several mechanisms to explain the cholesterol-lowering effect of beta-glucan. One hypothesis proposes that beta-glucan increases bile acid synthesis by binding to bile acids in the intestine. [15,16] Alternatively, it is possible that the viscous beta-glucan acts as a physical barrier in the intestine, blocking absorption of bile acids and cholesterol. Other researchers have postulated that soluble fibers are bacterially fermented in the colon, leading to production of short-chain fatty acids, such as propionate, which may lower hepatic cholesterol synthesis.  Researchers also have suggested that, particularly after meals, soluble fibers lower insulin levels, which is known to lower cholesterol synthesis.  However, researchers have not found changes in serum cholesterol-precursor concentrations after oat consumption, suggesting that these latter two explanations are likely incorrect.
Numerous well-controlled trials did not demonstrate a beneficial effect of beta-glucan from oats on serum lipoprotein profile. [20, 21, 22, 23] Possible explanations for these inconsistent results may be differences in the viscosity of the beta-glucan or detrimental effects of food manufacturing on the viscous characteristics of beta-glucan. Elucidating the exact mechanism underlying the cholesterol-lowering effects of beta-glucan may help explain these apparent discrepancies.
In addition to the soluble fibers from oats, viscous fibers from other sources also may have favorable effects on serum lipoprotein profiles. Beta-glucan from barley and yeast, for example, appear to be effective. [24, 25]
Also in this respect, the FDA has approved a cholesterol-reducing health claim on psyllium, a soluble fiber isolated from the psyllium seed husk.  To achieve a significant reduction in total cholesterol levels, subjects must get at least 10.2 g PSH supplying 7 g soluble fiber daily (four servings each containing 1.7 g soluble fiber; 1 g weighs about as much as a paper clip) as part of a diet low in saturated fat and cholesterol. From three different meta-analyses, consumption of 910g PSH a day lowers serum LDL cholesterol concentrations by 6.0 percent to 7.4 percent. In contrast to beta-glucan, PSH-induced cholesterol reductions do not seem to be associated with initial cholesterol concentrations. [27, 28, 29]
Two characteristic fatty acids from fish are eicosapentaenoic acid and docosahexaenoic acid. Both EPA and DHA are highly unsaturated. Strictly speaking, these two fatty acids are not essential for humans, since we can synthesize EPA and DHA from alpha-linolenic acid found in vegetables. Synthesization rates, however, are low. 
Epidemiological studies do suggest that eating more fish has a protective effect, reducing CHD risk.  Indeed, researchers have demonstrated that EPA plus DHA lower fasting and postprandial serum triacylglycerol concentrations, especially in hypertriglyceridemic subjects; however, if anything, fasting serum LDL and HDL cholesterol concentrations increase slightly.  These effects on triglycerides are observed at intake levels that can hardly be achieved with regular foods. It is therefore questionable if the possible cardioprotective effect of fish oil can be fully explained by its effects on the serum lipoprotein profile. For example, EPA and DHA also affect other processes such as thrombotic function,  inflammation [34, 35] and modification of sodium channels to prevent ventricular fibrillation  and consequent sudden cardiac death. [37, 38]
Thus, although the evidence is compelling, it is still not known ifand at what intake levelsfish oil affects CHD risk and it is hard to ascertain because the precise mechanism of action is not known.
Diet Is The Cornerstone
Improving diet is an important step in improving an unfavorable lipoprotein profile, often decreasing LDL cholesterol levels an average of 10 percent to 15 percent. HDL cholesterol and triacylglycerol concentrations may be favorably affected, especially after weight loss. However, for those who do not achieve the desired lipoprotein profile despite strict dietary compliance, functional foods can be beneficial. Soy protein, beta-glucan and psyllium, in particular, are dietary components that may help reduce serum LDL cholesterol concentrations. Diets low in saturated fat, trans fatty acids and cholesterol, along with adequate amounts of soy protein and viscous fibers may lower LDL cholesterol concentrations by 30 percent to 35 percent. [39 ]
Sterols And Stanols Stand Tough
Ronald P. Mensink, Ph.D., is a professor in the department of human biology, Maastricht University, the Netherlands. Jogchum Plat, Ph.D., is an assistant professor and Daniëlle AJM Kerckhoff is a doctoral candidate.
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