Nuts for the Treatment of Hypercholesterolemia: Seeds of Change? 

By Susan T. Marcolina, MD, FACP

In today’s fat conscious world, the idea that a high-fat food could be good for your heath just seems nutty. Or does it? Recent research on the benefits of the Mediterranean diet has revealed that all fat is not equal in terms of its effects on cardiovascular health. Saturated fatty acids have been shown to elevate LDL cholesterol, an independent risk factor for coronary disease.1 Monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), including omega-3 polyunsaturated fats, on the other hand, are cardioprotective.2,3 Omega-6 and omega-3 fatty acids are essential fatty acids because they cannot be synthesized by humans and therefore must be ingested.

A key whole food source of MUFA and PUFA in the Mediterranean diet is nuts. Table 1 gives the fat grams contained in some common nuts.4

Table 1

Calories and fat in some common nuts4

Shelled nut (per ounce) Calories Total Fat (g) Saturated Fat (g) Monounsaturated Fat (g)  Polyunsaturated Fat (g)
Almonds (24 nuts) 170 14.5 1.5 10 3
Cashews (18 medium) 160 13 2.5 8 2.5
Macadamias (12 nuts) 200 20 2.5 16.5 1
Peanuts (a legume) (35 nuts) 160 13.5 2 7 4
Pecans (15 halves) 190 19 2 12 5
Pistachios (47 nuts) 160 14 2 8 4
Walnuts (14 halves) 180 18 2 5 11

Classification of Nuts

Nuts come from many different families of plants and are classified as either tree nuts (fruits with one seed in a hard shell) or peanuts, which are classified in the Leguminosae family along with peas and beans.4

Nutrient Composition of Nuts

Nuts are a veritable storehouse of protein, nutrients, and fats. Table 2 lists nut prices and important nutritional constituents. Nuts are an excellent source of the amino acid arginine, the dietary precursor of nitric oxide (NO), or endothelium-derived relaxing factor.5

Table 2

Nutritional constituents and cost of commonly eaten nuts4,5

Shelled Nut (per ounce) Vitamin E (mg) Folate (mcg) Dietary Fiber (g) Magnesium (mg) Copper (mg) Cost (per lb)
Almonds (24 nuts) 7 20 3.5 85 0.3 $4.99
Cashews (18 medium) 0.5 20 2 75 0.6 $5.99
Macadamias (12 nuts) 0.1 2 30 0.4 $6.99
Peanuts (a legume) (35 nuts) 2 30 2 50 0.3 $2.29
Pecans (15 halves) 1 10 2 35 0.3 $5.99
Pistachios (47 nuts) 2 15 3 45 0.3 $3.33
Walnuts (14 halves) 0.7 19 3 50 0.4 $4.99

Mechanism of Action

At least five mechanisms may exist by which nuts lower total cholesterol levels. NO is a potent endogenous vasodilator and interrupts the atherogenic process by inhibition of platelet adhesion, platelet aggregation, vascular smooth muscle cell proliferation, monocyte adherence, and chemotaxis.6 Nuts are also one of the best natural sources of the antioxidant vitamin E, which attaches to LDL molecules and inhibits the propagation of lipid peroxidation, an essential step in the pathogenesis of atherosclerosis.7

Nuts are one of the main food sources of copper and magnesium, both of which have been shown to be protective for coronary heart disease (CHD): Supplementation of magnesium in the clinical setting of an acute myocardial infarction is protective against specific ventricular arrhythmias.8,9 Nuts contain large amounts of dietary fiber, which lowers cholesterol.10 Finally, the folic acid content of nuts may help to lower homocysteine levels; hyperhomocysteinemia has been linked to increased atherosclerosis.11

Clinical Studies: CHD

Four large prospective cohort studies (The Adventist Health Study, the Iowa Women’s Health Study, the Nurses’ Health Study, and the Physicians’ Health Study) examined the relationship between the consumption of nuts and CHD risk. All found an inverse association.

The Adventist study followed 26,473 healthy white nondiabetic subjects for six years. It showed that subjects who consumed nuts frequently (greater than five times per week) had an approximately 50% lower risk of either a fatal or nonfatal coronary event than those who ate nuts rarely (less than once per week). This risk reduction persisted despite adjustment for sex, age, smoking, exercise, relative weight, hypertension, and consumption of foods such as vegetables and white or whole grain breads.

Fraser et al evaluated 1,668 African-American Adventists and reported a lower total mortality in the segment of this population that consumed nuts more frequently.12 A dietary substudy of 147 randomly selected local subjects from the same cohort showed that 32% of the nuts consumed were peanuts, 29% were almonds, 16% were walnuts, and 23% were other nuts.

The 34,000 postmenopausal women ages 55-60 in the Iowa Women’s Study showed a 40% reduction in risk of fatal and nonfatal coronary events with higher nut consumption, despite the fact that the highest category was 2-4 times per week.13

Hu et al examined the association between CHD (fatal or nonfatal) incidence and nut consumption in a cohort of 84,409 women from the Nurses’ Health Study.14 Nut consumption was assessed at baseline and during a 14-year follow up. The women who ate 1 ounce of nuts five times or more per week had a significantly decreased risk of CHD than those who consumed less than 1 ounce per month with a relative risk of 0.65 (P for the trend = 0.0009).

The Physicians Health Study found a significantly decreased risk of cardiac death among 22,000 male physicians as nut consumption increased.15 This trend persisted after adjustment for cardiac risk factors.

Clinical Studies: Lipids

Spiller et al conducted a randomized, controlled parallel-design study in 45 free-living hyperlipidemic men (12) and women (33) with a mean plasma total cholesterol of 251 mg/dL to assess the effects of three different fat-containing diets on serum lipid profiles.16 Twelve subjects consumed the dairy-based fat control diet composed of 85 g of cheddar cheese and 28 g of butter. The 15 subjects in the olive oil group consumed 48 g of olive oil and the 18 subjects in the almond group received 100 g (3.4 ounces) of almonds supplied as whole and ground nuts. The protein and carbohydrate content of the diets were all similarly adjusted. After four weeks, there were highly significant reductions in total cholesterol (TC) (P < 0.05), LDL cholesterol (P < 0.001), and TC/HDL ratio (P < 0.001) in the almond-based diet, despite a total fat intake 9 g higher than recommended by the National Cholesterol Education Program for lowering cholesterol. There were no significant weight changes over the time of the study period.

Hyson et al performed a randomized crossover dietary intervention trial on 22 normocholesterolemic, nonsmoking, healthy men and women using a whole almond (66 g or about 2.3 ounces) or almond oil (35 g) fat replacement.17 Although there were significant reductions in total and LDL cholesterol (4% and 6%, respectively) after the six weeks of almond product consumption compared with baseline, there were no differences in lipid levels between the two almond products. Plasma triglyceride levels were significantly reduced, VLDL was slightly reduced and HDL cholesterol significantly increased by 4% with both products.

Zambon et al studied the effects of walnut substitution for monounsaturated fat on the serum lipid profiles of 49 nonsmoking, healthy men and women (mean age 56 years) with polygenic hypercholesterolemia in a randomized crossover trial.18 The control diet was Mediterranean without nuts. The walnut diet was similar to the control diet but walnuts (41-56 g or 1.4-1.9 ounces) partially replaced olive oil and other fatty foods. The mean TC level decreased by 9% during the walnut diet and by 5% with the control diet compared to baseline values. Similarly, the mean LDL cholesterol level decreased by 11.2% during the walnut diet and 5.6% during the control diet. The two diets did not differ with respect to their effects on HDL cholesterol, VLDL, or triglycerides. The mean LDL/HDL cholesterol ratio did not change during the control diet but decreased by 8% during the walnut diet. Interestingly, the walnut diet decreased levels of lipoprotein(a) by 9.1%; the control diet decreased these levels by 3.4% relative to baseline. This difference was significant in men only.

Curb et al conducted a randomized crossover trial of three 30-day diets in 30 free-living volunteers of diverse ethnicities ages 18-53 years.19 Each was fed a diet high in saturated fat (37% daily energy as fat), an AHA Step 1 diet (30% of energy from fat), and a macadamia nut-based (from 2.7-7.4 ounces) monounsaturated fat diet (37% of energy from fat) in random order. Compared with baseline values, the mean TC level was 5% lower in the AHA Step 1 diet and 6% lower for the macadamia nut diet subjects (P < 0.01 for both). Similarly, LDL cholesterol levels were 7% lower than baseline levels for both subjects in the AHA diet and the macadamia nut diet (P < 0.05). HDL cholesterol levels were 4.5% lower after the Step 1 and the macadamia nut diets. Triglyceride levels, however, were increased 14% after the Step 1 diet, but decreased 10% after the macadamia nut diet.

Edwards et al performed a similar controlled, randomized crossover feeding study with pistachios (2.4 ounces) and found decreases in total, LDL cholesterol, and triglycerides and and also found increases in HDL cholesterol.20

Dosage

In a randomized controlled, crossover study involving 27 hyperlipidemic men and women, Jenkins et al found a dose-response effect using both half-dose almonds (36.5 g or about 1.3 ounces) and full-dose whole almonds (73 g or about 2.5 ounces) substituted for dietary fat.21 Half-dose almonds and full-dose almonds produced reductions of 4.4% (P = 0.018) and 9.4% (P < 0.001), respectively, in LDL cholesterol compared to the control diet. Full-dose almonds alone produced significant reductions in lipoprotein(a) (P = 0.034) and oxidized LDL levels (P < 0.001).

Approximately 1 ounce of nuts daily confers a hypolipidemic effect.

Adverse Reactions

The most common side effects reported in studies include complaints of gastrointestinal bloating and cramping, which were temporary and generally subsided with increased fluid intake and consuming nuts throughout the day rather than eating them all at once.12,13 Symptoms may be more problematic in individuals with chronic diverticular disease and nut consumption should be avoided in these patients. Systemic anaphylactic reactions can occur in individuals sensitive to nut proteins and any nuts or nut products should be carefully avoided in this population.

Conclusion

There is good evidence from epidemiologic and clinical feeding studies to support the use of almonds, walnuts, pecans, pistachios, and macadamia nuts as cost-effective, tasty dietary sources of MUFA and PUFA in a heart healthy diet.

Recommendation

For patients without a history of systemic anaphylaxis to nut proteins or diverticular disease, tree nuts and peanuts have nutritional profiles well suited to lower the risk of CHD effectively. Suitable patients should be instructed to substitute 1 ounce of nuts for other dietary fats so that weight gain and gastrointestinal disturbances are minimized or eliminated.

Dr. Marcolina is a board-certified internist and geriatrician in Issaquah, WA.

References

1. Shekelle RB, et al. Diet, serum cholesterol, and death from coronary heart disease. The Western Electric Study. N Engl J Med 1981;304:65-70.

2. Mensink RP, et al. Effects of monounsaturated fatty acids v complex carbohydrates on serum lipoproteins and apoproteins in healthy men and women. Metabolism 1989;38:172-178.

3. Harper CR, et al. The fats of life: The role of omega-3 fatty acids in the prevention of coronary heart disease. Arch Intern Med 2001;161:2185-2192.

4. Dreher ML, et al. The traditional and emerging role of nuts in healthful diets. Nutr Rev 1996;54:241-245.

5. Pennington JAT, ed. Bowes and Church’s Food Values of Portions Commonly Used. 15th ed. Philadelphia, PA: JB Lippincott; 1989.

6. Palmer RM, et al. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 1987;327:524-526.

7. Steinberg D, et al. Beyond cholesterol: Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-924.

8. Eisenberg MJ. Magnesium deficiency and cardiac arrhythmias. N Y State J Med 1986;86:133-136.

9. Shechter M, et al. Beneficial effect of magnesium sulfate in acute myocardial infarction. Am J Cardiol 1990;66:271-274.

10. Anderson JW. Dietary fiber, lipids and atherosclerosis. Am J Cardiol 1987;60:17G-22G.

11. Selhub J, et al. Association between plasma homocysteine concentrations and extracranial carotid artery stenosis. N Engl J Med 1995;332:286-291.

12. Fraser GE, et al. A possible protective effect of nut consumption on risk of coronary heart disease. The Adventist Health Study. Arch Intern Med 1992;152: 1416-1424.

13. Prineas RJ, et al. Walnuts and serum lipids. N Engl J Med 1993;329:329.

14. Hu FB, et al. Frequent nut consumption and risk of coronary heart disease in women: Prospective cohort study. BMJ 1998;317:1341-1345.

15. Albert CM, et al. Nut consumption and the risk of sudden and total cardiac death in the Physician’s Health Study. Circulation 1998;98(Suppl 1):1-58.

16. Spiller GA, et al. Nuts and plasma lipids: An almond-based diet lowers LDL-C while preserving HDL-C. J Am Coll Nutr 1998;17:285-290.

17. Hyson DA, et al. Almonds and almond oil have similar effects on plasma lipids and LDL oxidation in healthy men and women. J Nutr 2002;132:703-707.

18. Zambon D, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hyper-cholesterolemic men and women: A randomized crossover trial. Ann Intern Med 2000;132:538-546.

19. Curb JD, et al. Serum lipid effects of a high monounsaturated fat diet based on macadamia nuts. Arch Intern Med 2000;160:1154-1158.

20. Edwards K, et al. Effect of pistachio nuts on serum lipid levels in patients with moderate hypercholesterolemia. J Am Coll Nutr 1999;18:229-232.

21. Jenkins DJA, et al. Dose response of almonds on coronary heart diseae risk factors: Blood lipids, oxidized low-density lipoproteins, lipoprotein(a), homocysteine, and pulmonary nitric oxide: A randomized, controlled, crossover trial. Circulation 2002;106:1327-1330.