Natural Foods Merchandiser

Nutritional Compounds To Support Cholesterol Reduction

Coronary heart disease 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.1

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.

Soy Isoflavones
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.4 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.5

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.6 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.6

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.7 Further, essentially the same findings were described in hypercholesterolemic postmenopausal women.8 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.9 Also, 80 mg isoflavones in supplement form did not induce significant cholesterol lowering in menopausal and perimenopausal women with normal cholesterol levels.10 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.

Viscous Fibers
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.11 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."12

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.13 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.17 Researchers also have suggested that, particularly after meals, soluble fibers lower insulin levels, which is known to lower cholesterol synthesis.18 However, researchers have not found changes in serum cholesterol-precursor concentrations after oat consumption, suggesting that these latter two explanations are likely incorrect.19

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.26 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

Fish Oils
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.30

Epidemiological studies do suggest that eating more fish has a protective effect, reducing CHD risk.31 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.32 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,33 inflammation34,35 and modification of sodium channels to prevent ventricular fibrillation36 and consequent sudden cardiac death.37,38

Thus, although the evidence is compelling, it is still not known if—and at what intake levels—fish 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

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.


1. Austin MA. Plasma triglyceride and coronary heart disease. Arterioscler Thromb 1991;11:2-14.

2. Grundy SM. United States cholesterol guidelines 2001: expanded scope of intensive low-density lipoprotein-lowering therapy. Am J Cardiol 2001;88:23J-7J.

3. Kraus RM, et al. AHA dietary guidelines. Revision 2000: a statement for health care professionals from the nutrition committee of the American Heart Association. Circulation 2000;102:2284-99.

4. FDA presentation;

5. Potter SM. Soy proteins and serum lipids. Curr Opin Lipidol 1996;7:260-4.

6. Anderson JW, et al. Meta-analysis of the effects of soy protein intake on serum lipids. New Engl J Med 1995;333:276-82.

7. Crouse JR, et al. A randomized trial comparing the effects of casein with that of soy protein containing various amounts of isoflavones on plasma concentrations of lipids and lipoproteins. Arch Intern Med 1999;159:2070-6.

8. Gardner CD, et al. The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Am J Clin Nutr 2001;73:728-35.

9. Baum JA, et al. Long-term intake of soy protein improves blood lipid profiles and increases mononuclear cell low-density lipoprotein receptor messenger RNA in hypercholesterolemic, postmenopausal women. Am J Clin Nutr 1998;68:545-51.

10. Nestel PJ, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol 1997;17:3392-8.

11. Braaten JT, et al. Oat b-glucan reduces blood cholesterol concentrations in hypercholesterolemic subjects. Eur J Clin Nutr 1994;48:465-74.

12. FDA Talk Paper;

13. Ripsin CM, et al. Oat products and lipid lowering. A meta-analysis. JAMA 1992;267:3317-25.

14. Davidson MH, et al. The hypocholesterolemic effects of beta-glucan in oatmeal and oat bran. JAMA 1991;265:1833-9.

15. Kritchevski D, Story JA. Binding of bile salts in vitro by non-nutritive fiber. J Nutr 1974;104:458-64.

16. Bell S, et al. Effect of beta-glucan from oats and yeast on serum lipids. Crit Rev Food Sci Nutr 1999;39:189-202.

17. Thacker PA, et al. Influence of propionic acid on cholesterol metabolism of pigs fed hypercholesterolemic diets. Can J Anim Sci 1981;61:969-75.

18. Bourbon I, et al. Postprandial lipid, glucose, insulin and cholecystekonin responses in men fed barley pasta enriched with beta-glucan. Am J Clin Nutr 1999;69:55-63.

19. Uusitupa MI, et al. Lathosterol and other non-cholesterol sterols during treatment of hypercholesterolemia with beta-glucan-rich oat bran. Eur J Clin Nutr 1997;51:607-11.

20. Lovegrove JA, et al. Modest doses of b-glucan do not reduce concentrations of potentially atherogenic lipoproteins. Am J Clin Nutr 2000;72:49-55.

21. Torronen R, et al. Effects of an oat bran concentrate on serum lipids in free-living men with mild to moderate hypercholesterolemia. Eur J Clin Nutr 1992;46:621-7.

22. Beer MU, et al. Effects of oat gum on blood cholesterol levels in healthy young men. Eur J Clin Nutr 1996;49:274-5.

23. Leadbetter J, et al. Effects of increasing quantities of oat bran in hypercholesterolemic people. Am J Clin Nutr 1991;54:841-5.

24. McIntosh GH, et al. Barley and wheat foods: influence on plasma cholesterol concentrations in hypercholesterolemic men. Am J Clin Nutr 1991;53:1205-59.

25. Nicolosi R, et al. Plasma lipid changes after supplementation with b-glucan fiber from yeast. Am J Clin Nutr 1999;70:208-12.

26. FDA Talk Paper:

27. Olson BH, et al. Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis. J Nutr 1997;127:1973-80.

28. Brown L, et al, Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69(1):30-42.

29. Anderson JW, et al. Cholesterol-lowering effects of psyllium intake adjunctive to diet therapy in men and women with hypercholesterolemia: analysis of 8 controlled trials. Am J Clin Nutr 2000;71:472-9.

30. Vermunt SH, et al. Effects of dietary alpha-linolenic acid on the conversion and oxidation of 13C alpha-linolenic acid. Lipids 2000;35(2):137-42.

31. De Deckere EA, et al. Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin. Eur J Clin Nutr 1998;52:749-53.

32. Kromhout D, et al. The inverse relation between fish consumption and 20-year mortality from coronary heart disease, N Engl J Med 1985;312:1205-9.

33. Harris WS. n-3 Fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65 (Suppl.):1645S-54S.

34. Knapp HR. Dietary fatty acids in human thrombosis and haemostasis. Am J Clin Nutr 1998;65:s1687-s98.

35. De Caterina R, et al. Fatty acid modulation of endothelial activation. Am J Clin Nutr 2000;71 (suppl 1):213s-23s.

36. Endres S, et al. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumour necrosis factor by mononuclear cells. N Engl J Med 1989;320:265-71.

37. Das UN. Beneficial effects of n-3 fatty acids in cardiovascular diseases: but why and how? Prost Leko, Ess Fatty Acids 2000;63:352-62.

38. Albert CM, et al. Fish consumption and risk of sudden cardiac death. JAMA 1998;279:23-8.

39. Jenkins DJA, et al. Viscous fibers, health claims and strategies to reduce cardiovascular risk. Am J Clin Nutr 2001;71:401-2.

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Sterols And Stanols Stand Tough

Fruits and vegetables contain health-promoting compounds called phytosterols, specifically sterols and stanols. These compounds have been investigated since the 1950s for their cholesterol-lowering effects and, as such, are some of the earliest functional food ingredients. In results of a recent meta-analysis, plant sterols and stanols lowered LDL cholesterol concentrations in a dose-dependent way. HDL cholesterol and triacylglycerol concentrations were not affected. The maximum effect on LDL cholesterol of 9 percent to 14 percent was reached when intake was between 2 and 2.5g/day.1 These effects were not dependent on dietary cholesterol intake,2 use of cholesterol-lowering medication3 or apoE genotype.4,5 Researchers theorize that diabetic subjects may benefit from plant stanol esters consumption.6

These and other findings support the FDA-authorized health claim interim final rule stating, "A diet low in saturated fat and cholesterol including two servings of foods containing plant sterol or stanol esters—supplying at least 1.3 plant sterols or 3.4 g plant stanols a day—may reduce the risk of heart disease."7


1. Law M. Plant sterol and stanol margarines and health. BMJ 2000;320:861-4.

2. Vanhanen HT, et al. Serum cholesterol, cholesterol precursors and plant sterols in hypercholesterolemic subjects with different apoE phenotypes during dietary sitostanol-ester treatment. J Lipid Res 1993;34:1535-44.

3. Blair S, et al. Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin treatment. Am J Cardiol 2000;86:46-52.

4. Plat J, Mensink RP. Vegetable oil-based versus wood-based stanol ester mixtures: effects on serum lipids and hemostatic factors in non-hypercholesterolemic subjects. Atherosclerosis 2000;148:101-12.

5. Hallikainen MA, et al. Plant stanol esters affect serum cholesterol concentrations of hypercholesterolemic men and women in a dose-dependent manner. J Nutr 2000;130:767-76.

6. Gylling H, Miettinen TA. Serum cholesterol and lipoprotein metabolism in hypercholesterolemic NIDDM patients before and during sitostanol ester-margarine treatment. Diabetologia 1994;37:773-80.

7. FDA Talk Paper;


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