Dietary Therapy to Reduce Cardiovascular Disease:

There is little doubt that high levels of low-density lipoprotein cholesterol (LDL-C) are a risk factor for the development of coronary artery disease (CAD). As populations in western countries become older, heavier, and more sedentary, the incidence and prevalence of vascular disease will continue to rise; hence, the need for aggressive measures to control levels of LDL-C.

The combination of an aging citizenry and the rising prevalence of obesity affects countries around the world. In Japan and Italy, more than 20% of the population will be 65 years or older in the next decade (although both lag far behind the United States in obesity prevalence), whereas the United States will not reach this point for more than a generation. In China, rising prosperity has translated into dramatic dietary shifts, particularly in urban areas, as well as increased use of automobiles. This combination will provide an "experiment of nature" as more Chinese persons experience overweight, diabetes, or CAD.

Although a number of effective LDL-C–lowering drugs exist, only a small percentage of patients with CAD and those at increased risk are receiving treatment that follows the guidelines established by the National Cholesterol Education Program. Perhaps now is the time to reemphasize the central role of non-pharmacologic-especially dietary-approaches to lowering LDL-C levels. When consistently and conscientiously applied, these changes can significantly improve lipid profiles, as well as reduce the costs of lipid-lowering therapy and the incidence of drug-related side effects. In this article, I outline the dietary measures that effectively reduce LDL-C levels and associated cardiovascular risk.

DIETARY STRATEGIES FOR DYSLIPIDEMIA

Dietary measures to reduce both LDL-C levels and the accompanying risk of CAD are much more effective than once believed (Table 1).¹ The primary strategy is a qualitative change in the diet that consists of reducing saturated fat and cholesterol. Evidence shows that the following dietary measures can also help lower LDL-C levels:

•Consumption of significant amounts of a variety of soluble fibers.

•Addition of plant sterol and stanol esters to the diet.

•Supplementation with a variety of nuts.

•Substitution of soy protein for meat protein.

Pessimism about the role of diet may have come from the fact that modest reductions in dietary cholesterol and saturated fat, as prescribed by the National Cholesterol Education Program guidelines, typically reduce LDL-C concentration by only about 5%, with a corresponding reduction in high-density lipopro-tein cholesterol (HDL-C) levels,²although better effects have been obtained in studies that use prepared foods and in which participants are monitored intensively.³ Low-fat vegetarian diets are substantially more effective because of the absence of cholesterol, the very low concentration of saturated fat, and the high fiber content of plant-derived foods. In one study of hyperlipidemic persons with cardiovascular disease who were treated for 1 year with a low-fat vegetarian diet and a program of mild exercise, stress management, and smoking cessation, serum LDL-C concentrations fell 37%, and angiographic evidence of reversal of atherosclerotic lesions was found in 82% of participants.⁴ Another study in healthy premenopausal women showed that a low-fat vegetarian diet reduced mean serum LDL-C levels by 17% in 8 weeks.⁵ This effect was independent of exercise.

Although low-fat vegetarian diets may appear spartan at first glance, their acceptability is similar to that of less rigorousdiets, and their effectiveness in reducing lipids, weight, and blood pressure facilitates long-term adherence.⁶ For some patients, especially those with elevated triglyceride levels, a moderately fatty diet with emphasis on unsaturated fats may be preferable.

Low-carbohydrate fad diets are not recommended for cholesterol control. Although weight reduction by any means is typically associated with approximately a 1 mg/dL reduction in total cholesterol per pound lost,⁷ low-carbohydrate diets result in an increase in LDL-C levels-sometimes to a dramatic degree-in approximately 30% of dieters.⁸

SOLUBLE FIBER

Soluble fiber has long been known to lower serum cholesterol concentrations, although it is not routinely recommended by clinicians. The term "soluble"fiber refers to water-soluble properties of nondigestible carbohydrates; some prefer the term "viscous"fiber. A daily intake of 25 to 30 g of dietary soluble fiber is recommended, but only a small percentage of community-dwelling adults consume this amount regularly (Table 2).

A 1999 study of 2900 adults noted that dietary fiber had a negative linear relationship from the lowest to the highest quintile for weight; waist-to-hip ratio; fasting insulin; blood pressure; and LDL-C, triglyceride, and fibrinogen levels.⁹ Similarly, the Nurses Health Study of 75,000 women noted an inverse relationship between whole-grain intake and CAD.¹⁰

Soluble fibers include pectin, psyllium (Plantago ovata) (a seed husk plant native to Iran and India that contains 70% soluble fiber, much more than oat bran, which has about 5% B-glucan), and B-glucan from yeast, guar gum, and rye bread. Soluble fiber appears to lower LDL-C by increasing bile acid loss, interrupting enterohepatic circulation of cholesterol, and reducing hepatic cholesterol delivery by chylomicron remnants.¹¹

The method and timing of psyllium ingestion play a role in its effectiveness. In one study, when psyllium was ingested as a cereal, it reduced total cholesterol levels by 8% within 3 to 4 weeks, but it was much less effective when given between meals.¹²

In another study, a fiber-multivitamin combination that contained 4.5 g of soluble fiber derived from guar gum, pectin, oat bran, barley, gum acacia, folate, and B vitamins, reduced LDL-C levels by 8% in 8 weeks.¹³ Two packets of the mixture are required daily.

PLANT STANOLS AND STEROLS

Foods containing stanol or sterol esters lower cholesterol concentrations. A meta-analysis of more than 40 published trials showed a consistent lowering of LDL-C levels with the addition of plant stanols or sterols to the diet (in margarine, mayonnaise, or olive oil).¹⁴ The absolute reduction in LDL-C level increases with a patient's age, as does the baseline LDL-C level. The maximum effectiveness is an LDL-C reduction of about 11%, and there is little additional benefit beyond a dosage of 2 g/d. Stanols and sterols have comparable effects; neither has a major effect on HDL-C or triglyceride levels. The response curve of apolipoprotein B is similar to that of LDL-C, which suggests that LDL-C is lowered by a reduction in the number of particles, rather than by a change in size or composition. The LDL-C–lowering effect is similar whether the dose is given once daily or more frequently.

The effects of stanols and sterols appear to be additive to the effects of other components of the diet,as well as to the effects of statins. The 10% reduction in LDL-C level is likely to reduce CAD risk by 20% over a lifetime. This effect is greater than that achieved by doubling the standard dose of statins.

NUTS

Studies during the past decade have demonstrated that nut consumption is associated with a reduction in LDL-C levels as well as in the number of cardiovascular disease risk factors. A disadvantage of nuts is their high fat content and resulting concentrated calories.

A randomized, cross-over, controlled study of the effect of almond consumption on serum lipid levels included 27 hyperlipidemic adults who ingested 3 isocaloric supplements (mean, 423 kcal/d) for 1 month.¹⁵ The dose-response effect of almonds was compared with that of whole wheat muffins low in saturated fat. The supplements provided 22% of daily energy requirements as full-dose almonds, half-dose almonds and half-dose muffins, and full-dose muffins.

Consumption of full-dose almonds (73 g) resulted in the largest reduction in LDL-C (9%), as well as reductions in lipoprotein (a) and oxidized LDL-C concentrations. Consumption of half-dose almonds was associated with a 4% reduction in LDL-C levels but no significant change in the lipoprotein (a) or oxidized LDL-C levels.

The effect of nuts on endothelial cells has broadened interest in their use for cardiovascular risk factor reduction. Endothelial dysfunction occurs early in the development of vascular disease, even before macroscopic changes are evident on radiographs, and is associated with atherosclerosis. Vascular reactivity is improved by substances such as omega-3 fatty acids, antioxidants, and arginine, all of which are found in walnuts.

In a cross-over study, 21 adults with hypercholesterolemia were randomized to a cholesterol-lowering Mediterranean diet or a diet of similar energy and fat content in which walnuts replaced approximately one third of the energy from monounsaturated fat.¹⁶ Eighteen of the participants had ultrasonographic measurements of the brachial artery before and after the dietary interventions. Compared with the Mediterranean diet, the walnut diet improved endothelial-dependent vasodilatation and levels ofvascular cell adhesion molecule-1. The cardioprotective effects of nuts such as walnuts may be explained in part by these vascular changes. In addition, LDL-C levels were reduced by 6%.

Combined data from a study that examined the effects of nut consumption on the risk of a cardiac event¹⁷ and other studies that have demonstrated reductions of 8% to 12% in LDL-C levels when almonds and walnuts are substituted for the traditional fats in a typical diet suggest that eating nuts is associated with a 30% to 50% reduction in CAD risk.

In the Physicians' Health Study, a cohort of 21,500 physicians, 20% of whom never or rarely consumed nuts, were followed for 17 years.¹⁸ Physicians who ate nuts 2 or more times per week experienced a statistically significant reduction in sudden cardiac death compared with the group who never ate nuts. Although it is possible that the nut-consuming physicians enjoyed a healthier lifestyle, it is also true that the nature of the follow-up of 350,000 participant-years of study provides a unique opportunity to examine nut consumption in a group of health professionals that will be difficult to duplicate in the future.

SOY PROTEIN

A newer approach to the use of nonpharmacologic therapy for hyperlipidemia was presented in 2003.¹⁹ The investigators chose 25 healthy adults who had elevated LDL-C levels but no vascular disease; they were not taking lipid-lowering drugs. The participants consumed a vegetarian diet-termed the "portfolio diet"-that provided 1.2 g of plant sterols, 8 g of viscous fiber, 16 g of almonds, and 16 g of soy protein per 1000 calories. Compliance was monitored with weekly checklists and the return of uneaten foods supplied by the investigators. The portfolio diet produced a 35% reduction in LDL-C levels with no significant weight changes during the 4-week test. This reduction was similar to that obtained with starting doses of statin drugs, and demonstrated the additive effect of a variety of foods known to lower LDL-C levels in the setting of a low-fat baseline diet.

In a more recent and significant study, the same researchers investigated a group of 46 healthy hyperlipidemic adults.²⁰ The participants were randomly assigned to undergo 1 of 3 interventions as outpatients for 1 month: a cereal-based diet very low in saturated fat ("control" diet); the same diet plus lovastatin, 20 mg/d; or the portfolio diet. Measurements of blood pressure, C-reactive protein (CRP), and blood lipids were compared. The control, statin, and portfolio groups had mean LDL-C reductions of 8%, 31%, and 28.6% and mean reductions in CRP of 10%, 33%, and 28%, respectively. There were no significant differences in efficacy between the statin and portfolio diet treatments. The authors calculated that the coronary heart disease risk in the portfolio diet and statin groups was reduced by 25%, compared with 3% in the control group.

Past meta-analysis has indicated an LDL-C reduction of 6% to 7% for 10 g/d of psyllium, 13% for 1 to 2 g/d of plant sterols, 12% for 45 g/d of soy protein, and 1% for 10 g/d of almonds. In light of the low-fat baseline diet, an LDL-C reduction of 4% to 7% is more appropriate and would equal the total 28% reduction observed.

The reduction in CRP achieved with the portfolio diet is similar to that achieved with statins and is not related to the reduction in LDL-C. The different modes of action of the elements in the portfolio diet may contribute to the additive effect. Viscous fibers increase bile acid losses, plant sterols reduce cholesterol absorption, and soy proteins reduce hepatic cholesterol synthesis. Almonds contain monounsaturated fatty acids as well as plant sterols. This controlled study demonstrates the additive effects of the various dietary components in the presence of a low-fat, cholesterol-free diet.²⁰

Additional dietary interventions are being explored, including the use of dark chocolate, green tea, and other foods.^21,22 However, it is abundantly clear that dietary management is an essential part of the treatment of lipid disorders.^1,23 In addition to its effects on lipids, a plant-based diet is likely to be less expensive than a diet based on animal products or a drug regimen,and it may reduce weight, blood pressure, and other cardiovascular risk factors. n

References:

REFERENCES:

1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106: 3143-3421.

2. Hunninghake DB, Stein EA, Dujovne CA. The efficacy of intensive dietary therapy alone or combined with lovastatin in outpatients with hypercholesterolemia. N Engl J Med. 1993;328:1213-1219.

3. Lichtenstein AH, Ausman LM, Jalbert SM, et al. Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects. J Lipid Res. 2002;43:264-273.

4. Ornish D, Brown SE, Scherwitz LW, et al. Can

lifestyle changes reverse coronary heart disease?

Lancet. 1990;336:129-133.

5. Barnard ND, Scialli AR, Bertron P, et al. Effectiveness of a low-fat, vegetarian diet in altering serum lipids in healthy premenopausal women. Am J Cardiol. 2000;85:969-972.

6.Barnard ND, Scherwitz LW, Ornish D. Adherence and acceptability of a lowfat, vegetarian diet among patients with cardiac disease. J Cardiopulmonary Rehabil. 1992;12:423-431.

7. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320-328.

8. Yancy WS, Olsen MK, Guyton JR, et al. A low-carbohydrate, ketogenic diet versus a low-fat diet to treat obesity and hyperlipidemia. Ann Intern Med. 2004;140:769-777.

9. Ludwig DS, Pereira MA, Kroenke CH. Dietary fiber, weight gain and cardiovascular risk factors in young adults. JAMA. 1999;282:1539-1546.

10. Lui S, Stampfer FB, Hue HB. Whole-grain consumption and the risk of coronary heart disease: results from the Nurses Health Study. Am J Clin Nutr. 1999;70:412-419.

11. Fernandez ML. Soluble fiber and nondigestible carbohydrate effects on plasma lipids and cardiovascular risk. Curr Opin Lipidol. 2001;12:35-40.

12. Wolever TM, Jenkins DJ, Mueller S, et al. Method of administration influences the serum cholesterol-lowering effect of psyllium. Am J Clin Nutr. 1994;59:1055-1059.

13. Sprecher DL, Pearce GL. Fiber-multivitamin therapy. Metabolism. 2002;51:1166-1170.

14. Katan MB, Grundy SM, Jones P, et al. Efficacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc. 2003;78:965-978.

15. Jenkins DJA, Kendall CWC, Marchie A, et al. Dose response of almonds on coronary heart disease risk factors: blood lipids, oxidized low-density lipoproteins, lipoprotein (a), homocysteine, and pulmonary nitric oxide. Circulation. 2002;106: 1327-1332.

16. Rose, Nunez I, Heras AP, et al. A walnut diet improves endothelial function in hypercholesterolemic subjects. Circulation. 2004;109:1609-1614.

17. Fraser GE. Nut consumption, lipids, and risk

of a coronary event. Clin Cardiol. 1999;22(suppl 7):III11-5.

18. Albert CA, Gaziano M, Willet WC, et al. Nut

consumption and decreased risk of cardiac sudden

death in the physicians' health study. Arch Intern Med. 2002;162:1382-1387.

19. Jenkins DA, Kendall CWC, Marchie A, et al. The effect of combining plant sterols, soy protein, viscous fibers and almonds in treating hypercholesterolemia. Metabolism. 2003;52:1478-1483.

20. Jenkins DJA, Kendall CWC, Marchie A, et al. Effects of a dietary portfolio of cholesterol-lowering foods vs lovastatin on serum lipids and C-reactive protein. JAMA. 2003;290:502-510.

21. Taubert D, Berkels R, Roesen R, Klaus W. Chocolate and blood pressure in elderly individuals with isolated systolic hypertension. JAMA. 2003;290: 1029-1030.

22. Chyu KY, Babbidge SM, Zhao X, et al. Differential effects of green tea-derived catechin on developing versus established atherosclerosis in apolipoprotein E-null mice. Circulation. 2004;109:2448-2453.

23. Anderson JW. Diet first, then medication for hypercholesterolemia. JAMA. 2003;290:531-533.