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Effect of Pistachio Nuts on Serum Lipid Levels in Patients with Moderate Hypercholesterolemia

Nephrology Division (K.E., I.K., I.K.), Bio-Statistics Department (J.M.), UCLA School of Medicine, Los Angeles, California

Address reprint requests to: Karen Edwards, M.S., 11444 West Olympic Boulevard, Los Angeles, CA 90064

	ABSTRACT

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Background: Elevated serum cholesterol levels play an important role in the development of coronary artery disease. Previous studies have suggested that nut consumption benefits lipid profile. Pistachio nuts are widely available, inexpensive and frequently consumed by the general population.

Objective: To determine whether substituting 20% of the daily caloric intake in the form of pistachio nuts will improve the lipid profiles of humans with primary, moderate hypercholesterolemia.

Design: Controlled, randomized crossover design.

Setting: Outpatient dietary modification, counseling and blood analysis.

Patients: Ten patients with moderate hypercholesterolemia.

Intervention: Three weeks of dietary modification with 20% caloric intake from pistachio nuts.

Measurements: Body weight, blood pressure, total cholesterol, LDL, HDL, and triglycerides were monitored. Lipid profiles were analyzed prior to, during and after dietary modification.

Results: After three weeks, there was a decrease in total cholesterol (p<0.04), an increase in HDL (p<0.09), a decrease in the total cholesterol/HDL ratio (p<0.01) and a decrease in the LDL/HDL ratio (p<0.02). Triglycerides and LDL levels decreased, but not significantly. Body weight and blood pressure remained constant throughout the study.

Conclusions: Results suggest that eating pistachio nuts instead of other dietary fat calories can improve lipid profiles, thereby decreasing coronary risk. Further studies will be required to confirm these results and to determine the mechanism of this effect.

Key words: pistachio nuts, hypercholesterolemia, lipids, cardiac risk

	INTRODUCTION

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Epidemiologic studies have shown that diets with a high monounsaturated fat to saturated fat ratio and polyunsaturated fat to saturated fat ratio seem to bring about lower serum cholesterol levels and reduce the incidence of coronary artery disease [1,2]. Current research suggests that diets high in polyunsaturated fat are potentially carcinogenic, especially for carcinoma of the breast in women [3].

Recently, a number of studies have reported the beneficial effects of nuts, especially almonds and walnuts, on serum lipid levels and subsequent coronary artery disease (CAD) [4–7]. The specific mechanism or mechanisms determining these improved lipid profiles and reduced risk of CAD are unknown, but may be related to the unsaturated fat content [2,8,9]. Although all nuts have high levels of either mono (M) or polyunsaturated (P) fats and low levels of saturated (S) fats, the fatty acid composition of each type of nut varies [10] (Fig. 1). Additionally, nuts are generally high in vitamin E and fiber, characteristics which would make them healthier alternatives to snack foods such as microwave popcorn, buttered popcorn, most candy bars, potato chips and the like. The benefit of nuts has been attributed to their high level of polyunsaturated fats, a high P/S ratio, and their high monounsaturated fat content [2,7–9] (Table 1).

View larger version (88K): [in this window] [in a new window]   Fig. 1. Fatty acid content of selected nuts (grams per one ounce serving).

	METHODS

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Patient Selection
Subjects were obtained by physician referral. They included a group of four men (ages forty-one to fifty-three) and six women (ages twenty-eight to sixty-four); the median age was forty-six years. All subjects had moderate hypercholesterolemia (serum cholesterol greater than 210 mg/dL). The range was 214 mg/dL to 336 mg/dL with a median of 243 mg/dL. Subjects’ median weight was 66.9 kg with a range of 49.8 to 101.8 kg. Median blood pressure was 120/78 mm Hg with systolic values ranging from 98 to 140 mm Hg and diastolic values ranging from 50 to 100 mm Hg.

Excluded from the study were those patients with renal failure (creatinine greater than 1.5) and those patients being treated for hyperlipidemia. Patients with secondary hyperlipidemia due to diabetes mellitus, hypothyroidism, nephrotic syndrome, dysglobulinemias, Cushing’s syndrome or acute intermittent prophyria were excluded; in addition, patients on glucocorticoids or estrogen therapy were excluded. Patients with hypertension and angina were also excluded. No patients were on medications, including beta blockers and thiazide diuretics. Smokers were not excluded; however, no subject smoked. Although not excluded, no subject was a vegetarian. The subjects were asked to maintain similar physical activity and other lifestyle habits, and they kept diaries to record any signs of illness and to record any new medications taken. One patient was dropped from the study because he was inadvertently placed on thiazide diuretics.

Experimental Design
A controlled, randomized crossover design was utilized, and subjects served as their own controls. One half of the subjects were randomized to a pistachio group for three weeks, and the other half maintained their regular diets for three weeks. All subjects had their lipid profiles measured during an initial visit (baseline) and on days five and seven of the third week of each dietary period. The subjects were then crossed over and lipid profiles were remeasured in the same way. There was no lag time between the diet crossover. The experimental design was approved by the UCLA Human Subjects Protection Committee.

Dietary Intervention
Prior to the study period and prior to any scheduled meetings with the dietitian, the subjects were required to submit a consecutive three-day food record (the reference diet). Diets were analyzed for calorie and macronutrient (percentage of carbohydrates, fat, protein and fiber) content. Half of these patients were placed on a pistachio diet. This involved substituting roasted, unsalted pistachio nuts for 20% of their daily caloric intake. The subjects otherwise consumed the components of their regular diets. Subjects who normally consumed high fat snacks were instructed to substitute the pistachios nuts. If a subject did not normally consume high fat snacks, pistachio nuts were substituted as fat calories. Subjects kept one-day food records for each of the six weeks; these were analyzed to ensure that the subjects were consuming the appropriate quantities of pistachio nuts. Subjects met with the dietitian weekly to discuss the pistachio substitutions and were educated as to any necessary changes. After three weeks the subjects on the pistachio diets were crossed over to their regular diets, and the subjects on the regular diets were crossed over to the pistachio diet.

Measurements
The subjects were age, sex and weight matched. A dietitian calculated the daily caloric intake, including the quantity of saturated, monounsaturated and polyunsaturated fatty acids, protein, carbohydrate and fiber consumed by subjects on a weekly basis to ensure that the diets did not change significantly. Any signs of illness or any new medications taken were recorded in diaries.

Body weights as measured without shoes or heavy clothing were recorded the first three days during week one of the reference diet and the experimental diet and the first three days of week three at the end of each dietary period.

Following an overnight fast, 10 cc of venous blood samples were taken from an anticubital vein into evacuated tubes with 1.2 mg ethylene diaminetetra acetic acid (EDTA)/mL blood. The tubes were then immediately put into ice water. Within two hours, plasma was separated by centrifugation, 2500xg at 4°C and stored at -70°C prior to analysis. High density lipoprotein (HDL) was separated by sodium phosphotungstate precipitation of the low density lipoprotein (LDL) in the bottom fraction at d=1.006 g/ml. Cholesterol and triglycerides in plasma were determined by enzymatic methods. LDL was calculated by the method of Friedewald [11]. Blood was drawn on days one and three of the first week and days five and seven of the third week of each dietary period (reference diet and pistachio diet).

Statistical Analysis
The data were analyzed with the assistance of the Bio-Statistics Department of UCLA School of Medicine. Significance was determined by the exact Wilcoxon Signed Rank Test because the limited sample size did not allow for any assumptions regarding the normality of the sampling distribution. Two-sided p values are given.

	RESULTS

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The data are reported as the median change of each variable for the ten subjects. The lipid changes are summarized in Table 2. Total cholesterol fell from 243 mg/dL to 239 mg/dL (p<0.04). HDL cholesterol rose from 50 mg/dL to 56 mg/dL (p<0.09). LDL cholesterol fell from 180 mg/dL to 158 mg/dL, although the probability of this decrease was not statistically significant. Triglycerides fell from 113 mg/dL to 108 mg/dL, but, as it happened with the LDL, there was too much variation to obtain a significant p-value. The ratio of total cholesterol to HDL fell from 4.8 to 4.5 (p<0.01). The ratio of LDL/HDL cholesterol also fell, from 3.2 to 3.1 (p<0.04). There were no significant changes in body weight and blood pressure during the study.

	DISCUSSION

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A previous study by Fraser and colleagues [4] has demonstrated that the frequent consumption of nuts may protect against coronary artery disease, although no distinction was made between the type of nut ingested. Subsequent studies investigating the effect of walnuts by Sabaté and associates [5] and Abbey and colleagues [6] and the effect of almonds by Spiller and associates [7] demonstrated an improved lipid profile in healthy volunteers. Sabaté and colleagues [5] demonstrated a reduction in total cholesterol, LDL cholesterol, HDL cholesterol and LDL/HDL ratio. The study by Spiller and associates [7] detected significant changes in total cholesterol and LDL cholesterol only. The results of the present study compare favorably with these previous results. After only three weeks, subjects ingesting pistachio nuts had a significant decrease in total cholesterol, total cholesterol/HDL cholesterol, LDL/HDL cholesterol and an increase in HDL cholesterol. When comparing almonds and walnuts, Abbey and colleagues found a significant decrease in total cholesterol and LDL cholesterol; however, no changes in HDL cholesterol could be demonstrated. None of the studies (including the present study) detected any significant change in serum triglycerides.

The serum lipid parameters which are most predictive of subsequent coronary artery disease remain controversial. A recent study by Kinosian and colleagues [12] showed that changes in total cholesterol/HDL and LDL/HDL ratios were better predictors of coronary heart disease than changes in LDL alone. Pistachio nuts altered these important parameters (total cholesterol/HDL and LDL/HDL cholesterol) in the cardioprotective direction.

	CONCLUSION

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The substitution of pistachio nuts for other fat calories in the form of snacks for a consecutive three-week period can significantly improve the lipid profile in patients with moderate hypercholesterolemia. Further studies will be required to determine the mechanism achieving this effect and to document that the improved serum lipid profile decreases the risk of coronary artery disease.

Received May 1, 1998. Accepted December 1, 1998.

	REFERENCES

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1. Keys A: "Seven Countries. A Multivariate Analysis of Death and Coronary Heart Disease." Cambridge, MA: Harvard University Press, 1980.
2. Mattson FH, Grundy SM: Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man. J Lipid Red 26: 194–202, 1985.
3. Carroll KK, Hopkins, GJ: Dietary polyunsaturated fat versus saturated fat in relation to mammary carcinogenesis. Lipids 14: 155–8, 1979.[Medline]
4. Fraser GE, Sabaté J, Besson WL, Strahan TM: A possible protective effect of nut consumption on risk of coronary heart disease: the Adventist health study. Arch Intern Med 152: 1416–24, 1992.[Abstract]
5. Sabaté J, Fraser GE, Burke K, Knutsen SF, Bennett H, Lindsted K: Effects of walnuts on serum lipid levels and blood pressure in normal men. N Engl J Med 328: 603–7, 1993.[Abstract/Free Full Text]
6. Abbey M, Noakes M, Belling GB, Nestel PJ: Partial replacement of saturated fatty acids with almonds or walnuts lowers total plasma cholesterol and low-density-lipoprotein cholesterol. Am J Clin Nutr 59: 995–9, 1994.[Abstract/Free Full Text]
7. Spiller GA, Jenkins DJA, Cragen LN, Gates JE, Bosello O, Berra K, Rudd C, Stevenson M, Superko R: Effect of a diet high in monounsaturated fat from almonds on plasma cholesterol and lipoproteins. Am J Clin Nutr 11: 126–30, 1992.
8. Mensink RP, Katan MB: Effect of a diet enriched with monounsaturated or polyunsaturated fatty acids on levels of low-density and high-density lipoprotein cholesterol in healthy women and men. N Engl J Med 321: 436–441, 1989.[Abstract]
9. Reaven P, Parthasarathy S, Grasse BJ, Miller E, Almazan F, Mattson FH, Khoo JC, Steinberg D, Witztum JL: Feasibility of using an oleate-rich diet to reduce the susceptibility of low-density lipoprotein to oxidative modification in humans. Am J Clin Nutr 54: 701–6, 1991.[Abstract/Free Full Text]
10. Composition of foods: nuts and seed products. Agricultural handbook no. 8–12. Washington, DC: Department of Agriculture, 1984.
11. Friedewald WT, Levy RI, Fredrickson DS: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18: 499–502, 1972.[Abstract]
12. Kinosian B, Glick H, Preiss L, Puder KL: Cholesterol and coronary heart disease: predicting risks in men by changes in levels and ratios. J of Inves Med 43: 443–50, 1995.

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