Nuts Reduce Cardiovascular Disease Risk

By Amy E. Griel, PhD, and Penny M. Kris-Etherton, PhD, RD, Dr. Griel is a dietetic intern and Dr. Kris-Etherton is Distinguished Professor of Nutrition, Department of Nutritional Sciences, Penn State University, University Park, PA; Dr. Griel reports no consultant, stockholder, speaker's bureau, research, or other financial relationships with companies having ties to this field of study; Dr. Kris-Etherton receive research support from Hershey Foods and the California Pistachio Commission.

Part 2 of a Series on Cardiovascular Disease

[Note: Part 1 of this series appeared in the February issue of Alternative Medicine Alert and contained information on epidemiological and clinical nutrition studies as well as a discussion of results from clinical trials that specifically examined walnut consumption. This second part commences with a review of almonds.]

Almonds have been evaluated extensively and have been shown to lower total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) levels due to their nutrient content, including their fatty acid profile (they are a rich source of monounsaturated fatty acids [MUFA] and are low in saturated fatty acids [SFA]). As a result, almonds can be used as a fat source to achieve a moderate fat diet that is low in SFA. Almonds also contain a significant amount of α-tocopherol, a potent antioxidant, and many other proposed cardioprotective components, including folic acid, calcium, potassium, magnesium, copper, zinc, and specific phytochemicals.

To determine which individual components of almonds contribute to the reduction observed in lipids and lipoproteins, some studies have assessed whether the processing of almonds has an effect on the lipid-lowering effect. Comparing whole almonds vs. almond oil provides information about whether effects are due specifically to the oil fraction or whether there are benefits from both the fat and components of the total nutrient package. Employing a two-period six-week randomized crossover design, Hyson and colleagues tested whether the incorporation of whole almonds (66 g) vs. almond oil (35 g) into a habitual diet would have similar effects on blood lipids and lipoproteins.1 The only difference in the composition of the diets was a 36% increase in fiber with the incorporation of whole almonds, compared to both baseline and the almond oil diet. The incorporation of both whole almonds and almond oil diets significantly (P < 0.05) reduced TC (4%, 4%), LDL-C (6%, 7%), and triglycerides (TG, 14%, 15%), and increased high-density lipoprotein-cholesterol (HDL-C, 4%, 7%), respectively, compared to baseline. Thus, the results of this study indicate that the lipid-lowering effect of almonds is due primarily to the constituents in the lipid fraction of almonds, with no measurable added benefits from the non-lipid fractions.

A similar study tested the effects of incorporating 100 g of either roasted salted almonds, roasted almond butter, or raw almonds into a cholesterol-lowering diet.2 All three test diets were matched for total fat (~44%), SFA (~8%), MUFA (~22%), and PUFA (~10%). There was a significant reduction (P < 0.05) in LDL-C from all forms of almonds (12% for raw almonds and 7% for roasted almonds and almond butter); the reduction in TC was greatest following the raw almond diet (7%; P < 0.01) and similar for the roasted almond (5%; P < 0.05) and almond butter diets (5%). There were no significant changes in TG or HDL-C following the three different diets.

In addition to testing the different almond products, researchers also have evaluated the effects of incorporating almonds into a blood cholesterol-lowering diet on lipids and lipoproteins. When compared to a dairy-based diet (35% total fat, 17% SFA, 15% MUFA, and 3% PUFA), an almond-based diet (40% total fat, 5% SFA, 28% MUFA, and 7% PUFA) produced the greatest reductions in TC (16%) and LDL-C (19%) (P < 0.001).3 Within the context of a cholesterol-lowering diet, a dose-dependent relationship also has been observed with the consumption of increasing doses of almonds. Following the consumption of a Step II diet plus either 1) 73 g/d of whole almonds, 2) muffins, or 3) half portions of almonds (37 g/d) and muffins, a dose-response relationship was observed.4 The full portion of almonds was associated with a 5.6% reduction in TC, a 9.4% reduction in LDL-C, an 8.4% reduction in the ratio of TC:HDL-C, and a 3.8% increase in HDL-C, compared to baseline.

This dose-response effect was then tested by comparing the addition of two different levels of almond intake to a Step I diet.5 Twenty-five healthy individuals consumed a Step I diet (30% total fat), low-almond diet (35% total fat), and high-almond diet (39% total fat) in a randomized crossover study. Almonds represented 0%, 10% (~34 g/2,000 kcal), and 20% (~68 g/2,000 kcal) during the Step I, low-almond, and high-almond diets, respectively. Levels of TC, LDL-C, and apolipoprotein B, and the LDL-C:HDL-C ratio were reduced in a dose-response manner (TC: 5.41, 5.36, 5.17 mmol/L; LDL-C: 3.74, 3.70, 3.48 mmol/L, respectively, for Step-1, low-almond, and high-almond diets). There were no significant differences in levels of HDL-C or TG.

The results of these studies suggest that the incorporation of almonds into either a Step I or Step II diet will provide additional improvements to the lipid and lipoprotein profile, above those seen with the traditional Step I or Step II diet in a dose-dependent manner.

Macadamia Nuts

Macadamia nuts are a rich source of MUFA; thus, when they are substituted for other fats in the diet they can facilitate a shift to a fatty acid profile that is higher in MUFA and lower in SFA. To date, three clinical trials have evaluated the effect of macadamia nuts on the lipid and lipoprotein profile.

The results of a supplement trial by Garg et al show that the addition of macadamia nuts (40-90 g/d; 15% of the total energy intake), significantly decreased TC (3.0%) and LDL-C (5.3%), and increased HDL-C (7.9%) in hypercholesterolemic men.6

Two controlled feeding studies have demonstrated similar improvement in the lipid and lipoprotein profile following the incorporation of macadamia nuts into a cholesterol-lowering diet. In one study, investigators compared a high-carbohydrate diet (HCD; 21% total fat) and a macadamia-enriched diet (MD; 42% total fat) to the subjects' typical food intake (37% total fat).7 Both the HCD and MD elicited a significant reduction in TC (-7.9%) and LDL-C (-10.7%) when compared to typical food intake. The MD reduced TG levels by 20.9% and maintained levels of HDL-C; the HCD however elicited a 13.1% reduction in HDL-C.

In a later study, Curb et al compared a macadamia nut-based diet (37% total fat) to a typical American diet (37% total fat) and a Step 1 diet (30% total fat).8 Compared to the typical American diet, both the macadamia-based diet and the Step 1 diet reduced TC (5%, 4%; P < 0.01), LDL-C (4%, 5%; P < 0.05), and HDL-C (4%; P < 0.01, 6%; P < 0.001), respectively. TG levels were higher on the Step 1 diet (8%; P < 0.05), when compared to the typical American diet; however, the macadamia nut diet significantly reduced TG levels (9%; P < 0.05).

Pecans

Pecans are a rich source of MUFA and contain a number of cardioprotective compounds, including plant sterols, vitamin E, folic acid, calcium, magnesium, phosphorus, zinc, vitamin A, and several B vitamins. In addition, one serving of pecans provides approximately 10% of the daily value for both zinc and fiber. To date, two controlled feeding trials have assessed the lipid-lowering effect of pecans in healthy and hypercholesterolemic individuals. When compared to a self-selected diet, an eight-week supplement of 68 g/d of pecans resulted in a 6% reduction in LDL-C.9

In a later study, Rajaram et al employed a two-period crossover design to study the cholesterol-lowering effect of pecans.10 When compared to a Step I diet, the pecan-enriched diet (72 g of pecans per 2,400 kcal) elicited a 10.4% reduction in LDL-C in hypercholesterolemic individuals. In addition to the substantial reduction in LDL-C, several other lipid and lipoprotein risk factors were affected, including TC (-6.7%), HDL-C (+5.6%), LDL-C:HDL-C (-15.7%), TG (-11.1%), apolipoprotein B (-11.6%), and lipoprotein(a) (-15.1%).

Pistachio Nuts

Pistachio nuts are low in SFA and rich in MUFA and cholesterol-lowering phytosterols. One serving (~30 g; approximately 49 nuts) of pistachios contains 13 g of total fat (of which only 1.5 g is saturated fat); more than 10% of the daily value for dietary fiber, vitamin B6, thiamin, phosphorus, and copper; and 61 mg plant sterols. To date, two studies have tested the cholesterol-lowering effects of pistachio nuts.

In a two-period, three-week randomized crossover study, researchers assessed the effects of a 100 g (20% energy) supplementation of pistachio nuts on plasma lipids and lipoproteins.11 When compared to a habitual diet (37% total fat, 11% SFA, 11% MUFA, and 5% PUFA), the pistachio-enriched diet (39% total fat, 8% SFA, 15% MUFA, and 7% PUFA) reduced LDL-C (-11%), TC (-3.7%), TC:HDL-C (-14.6 %), and LDL-C:HDL-C (-9.4%).

In a similar study, the substitution of pistachios for 20% of the daily caloric intake resulted in significant reductions in the ratios of TC:HDL-C and LDL-C:HDL-C (P < 0.001 and P < 0.01, respectively), and small nonsignificant reductions in TG and LDL-C.12 Because pistachios contain the highest levels of plant sterols among nuts it is likely that other mechanisms in conjunction with those associated with their fatty acid profile account for their blood cholesterol-lowering effects.

Hazelnuts

Hazelnuts contain about 91% MUFA, mostly oleic acid, and less than 4% SFA. Hazelnuts also contain many cardioprotective compounds, including fiber, vitamin E, arginine, folate, vitamin B6, calcium, magnesium, and potassium. To date, only one study has evaluated the effects of hazelnuts on blood lipids and lipoproteins. Nineteen individuals with Type 2 diabetes consumed a high-carbohydrate diet (60% carbohydrate, 25% total fat, 10% SFA, 10% MUFA, and 5% PUFA) for 30 days, followed by a 15-day washout period before consuming a hazelnut diet (40% carbohydrate, 45% total fat, 9% SFA, 27% MUFA, and 9% PUFA) for 30 days.13 LDL-C and TC were significantly reduced (P < 0.01) following the hazelnut diet (26%, 12%, respectively) compared to baseline. The high-carbohydrate diet significantly reduced LDL-C (16%; P < 0.01) and minimally reduced TC (5%) compared to baseline. The changes observed in apolipoprotein B (+7%, -8%), HDL-C (+2%, +8%), and TG (-12%, -16%) following the high-carbohydrate and hazelnut diets, respectively, were not significantly different when compared to baseline.

In a recent study 15 hypercholesterolemic men consumed either a control diet or the control diet supplemented with 40 g/d of hazelnuts, providing 11.6% of the total energy content of the diet.14 Compared with baseline, the hazelnut-enriched diet decreased the concentrations of TG and apolipoprotein B and increased HDL-C (P < 0.05). In addition there was a trend for a decrease in TC (5.2%) and LDL-C (3.3%).

Incorporating Nuts into a Healthy Eating Plan

There is a strong body of evidence that nut consumption is associated with a decrease in CVD risk, a result due in part to the beneficial effects their fatty acid profiles have on plasma lipids and lipoproteins. However, it is important to appreciate that nuts are a calorically dense food. The concern in recommending nut consumption lies in the appropriate incorporation of this food within the diet to prevent overconsumption of calories and weight gain. The clinical research summarized demonstrates that the incorporation of nuts into the diet elicits a favorable response on multiple CVD risk factors without causing weight gain in an experimental setting. What is important is whether weight control can be achieved when individuals are making self-selected food choices that include nuts. It is reassuring that epidemiologic studies show that individuals who consume nuts do not have a greater BMI than individuals who do not eat nuts.15 In fact, the epidemiologic studies show an inverse association between frequency of nut consumption and BMI.15

Data from the Continuing Survey of Food Intake by Individuals and Diet and Health Knowledge Survey from 1994 to 1996 were used to test for differences between peanut users and non-users for total energy and nutrient intakes, diet quality as measured by Health Eating Index (HEI) scores, and BMI.16 The HEI was significantly greater for peanut users (men 61.4, women 65.1, children 66.8) compared to non-users (men 59.9, women 64.1, children 64.7) for men (P < 0.01) and children (P < 0.001). Although total energy intake (over a two-day period) was significantly higher in all population groups of peanut users, mean BMI for peanut users was lower for all gender/age categories. These results demonstrated improved diet quality of peanut users, indicated specifically by the higher intakes of the micronutrients vitamin A, vitamin E, folate, calcium, magnesium, zinc, iron, and dietary fiber, and by the lower intake of saturated fat and cholesterol. In addition, despite a higher energy intake over a two-day period, peanut consumption was not associated with a higher BMI.

In a 24-week free-living weight-loss clinical study, Wien and colleagues evaluated the effect of incorporating 84 g/d of almonds into a formula-based low-calorie diet (LCD, 39% total fat, 3% SFA, 25% MUFA, and 11% PUFA) compared to a complex-carbohydrate formula-based LCD (18% total fat, 3% SFA, 5% MUFA, and 10% PUFA).17 Improvements were observed in the lipid profile following both the almond-enriched diet and the complex carbohydrate diet. While both groups did lose weight, the loss was greater (P < 0.0001) for the almond-enriched diet (18%), compared to the complex-carbohydrate diet (11%). Overall, the almond-enriched LCD produced a sustained and greater weight loss in comparison to the complex carbohydrate LCD, accompanied by similar improvements in lipid profile.

Maximal Cholesterol Lowering Achievable with a Portfolio Diet

Numerous clinical studies have demonstrated cholesterol-lowering effects of diets that contain nuts without an increase in body weight. For the maximal reduction of TC and LDL-C by diet, it is now evident that a total diet approach is necessary that not only emphasizes the lowest amount of saturated fat and cholesterol achievable, but also the incorporation of high levels of viscous fiber and plant sterols.

A study conducted by Jenkins et al showed that a vegetarian diet that was very low in saturated fat and cholesterol and high in plant sterols (1 g/1,000 calories), soy protein (21.4 g/1,000 calories), viscous fiber (9.8 g/1,000 calories), and almonds (14 g/1,000 calories) decreased LDL-C by approximately 30%, similar to that observed with low-dose statin therapy (20 mg/d).18,19 While this study used almonds, based on studies conducted to date, it would be predicted that other nuts could be substituted to achieve the same blood cholesterol-lowering outcome. The portfolio diet and low-dose statin therapy both significantly reduce C-reactive protein, now a recognized CVD risk factor, by 28% and 33%, respectively. Thus, tree nuts can be an important part of a blood cholesterol-lowering diet that elicits a maximal effect attainable by diet that is comparable to low-dose statin therapy without an increase in body weight.

Taking the Next Step: Cellular Mechanisms of Nuts and Their Components

Current dietary guidelines recommend inclusion of unsaturated fatty acids within the context of a nutritionally adequate diet that provides 20-35% of calories from total fat, with 5-10% recommended for PUFA.20 Nuts are a powerful tool in achieving the above fatty acid profile for the reduction of lipids and lipoproteins due in large part to their fatty acid profile. Recent research findings have demonstrated how PUFA exert their regulatory and metabolic effects on a host of biological systems including decreasing TG and fatty acid synthesis and increasing mitochondrial β-oxidation, as well as peroxisome β-oxidation.21 There is also keen interest in understanding the role of PUFA in oxidative stress and inflammation, key physiological processes in the development of atherosclerosis. Relative to the latter, the mechanisms by which linoleic acid (LA) and α-linolenic acid (ALA) affect inflammation need to be better understood. There is recent evidence that LA and ALA, as well as docosahexaenoic acid, decrease IL-6, IL-1β, and TNF-α gene expression, and nuclear factor-κB activation, whereas peroxisome proliferator-activated receptor-γ DNA binding activity was increased.22 These findings reinforce the need to learn more about the signal pathways that mediate the effects of PUFA on gene transcription in a variety of biological systems. Moreover, it will be important to clarify how individual PUFAs, including omega-6 and omega-3 fatty acids, regulate a variety of biological systems that affect chronic disease risk.

Qualified Health Claims for Tree Nuts and Walnuts

As a result of the scientific literature demonstrating cholesterol-lowering effects of diets that contain tree nuts and walnuts, the Food and Drug Administration has approved qualified health claims for tree nuts and walnuts. The qualified health claims are as follows:

For tree nuts: "Scientific evidence suggests but does not prove that eating 1.5 ounces per day of most nuts [, such as name of specific nut,] as part of a diet low in saturated fat and cholesterol may reduce the risk of heart disease." These health claims will help consumers make wise food choices that can reduce risk of CVD.

For walnuts: "Supportive but not conclusive research shows that eating 1.5 ounces per day of walnuts, as part of a low saturated fat and low cholesterol diet and not resulting in increased caloric intake, may reduce the risk of coronary heart disease. See nutrition information for fat [and calorie] content."

Brazil nuts, macadamia nuts, cashews, and some types of pine nuts are excluded from the qualified health claim due to their saturated fat content.

Conclusion

Epidemiologic evidence clearly demonstrates that nut consumption reduces the risk of CVD, Type 2 diabetes, and gallstone disease. Clinical studies consistently have demonstrated beneficial effects on lipids and lipoproteins, primarily a reduction in LDL-C, which reduces CHD risk. This effect has been demonstrated in different population groups, utilizing various study designs and methods without any increase in body weight. Thus, when nuts are incorporated into a healthy diet, there is an improvement in the lipoprotein profile and a subsequent decrease in CVD risk.

Current dietary guidelines for reducing risk of chronic diseases recommend inclusion of unsaturated fatty acids within the context of a nutritionally adequate diet that provides 20-35% of calories from total fat, with 5-10% recommended for PUFA.20 The Third Adult Treatment Panel of the National Cholesterol Education Program recommends a diet that provides 25-35% of calories from total fat with up to 10% coming from PUFA.23 All current dietary guidelines recommend a diet low in SFA (< 10% of calories)20 and less than 7% of calories.23-25 Nuts are a food source that can be used to achieve these dietary recommendations. Because nuts are a rich source of unsaturated fats and are low in saturated fats, they are an important tool for achieving the recommended fatty acid profile for lowering blood cholesterol levels, and favorably affecting TG and HDL-C to reduce CVD risk. There is emerging evidence that nut consumption beneficially affects markers of inflammation and LDL particle size thereby further decreasing CVD risk beyond that due to changes in lipids and lipoproteins. It is likely that future research will identify other bioactive compounds in nuts that confer additional health benefits.

Recommendation

The recommendation to consume 4-5 servings (1 ounce servings) per week will markedly reduce risk of CVD. Patients should be advised to substitute 1 ounce of nuts for 2 ounces of meat and/or 2 teaspoons of vegetable oil. In addition, patients should be encouraged to refer to the dietary recommendations at www.mypyramid.gov, which provide information about how to include nuts in a heart healthy diet. In the table below, the number of different nuts per 1 ounce serving is provided.

The effects on LDL-C likely will be small (up to 5% decrease) based on the change in the fatty acid profile (and maybe the decrease in dietary cholesterol) of the habitual diet due to substitution of nuts for food sources high in saturated fat. The decrease in LDL-C would be expected to occur within a two-week period.

The effects of nut consumption (30 g/d; ~ 1 ounce) on the primary prevention of CVD is being studied in a randomized controlled clinical trial by the PREDIMED Study Investigators. The beneficial effects of a Mediterranean diet with nuts (and with olive oil vs. a low-fat group) on CVD risk factors have been reported.26 The results of this first intervention study with nuts on CVD endpoints will be important to determine the extent to which nut consumption can reduce CVD morbidity and mortality.

References

1. 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.

2. Spiller GA, et al. Effects of plant-based diets high in raw or roasted almonds, or roasted almond butter on serum lipoproteins in humans. J Am Coll Nutr 2003;22:195-200.

3. 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.

4. Jenkins DJ, 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: A randomized, controlled, crossover trial. Circulation 2002;106:1327-1332.

5. Sabate J, et al. Serum lipid response to the graduated enrichment of a Step I diet with almonds: A randomized feeding trial. Am J Clin Nutr 2003;77:1379-1384.

6. Garg ML, et al. Macadamia nut consumption lowers plasma total and LDL cholesterol levels in hypercholesterolemic men. J Nutr 2003;133:1060-1063.

7. Colquhoun D, et al. Effects of a macadamia nut enriched diet on serum lipids and lipoproteins compared to a low fat diet. Food Australia 1996;48:216-222.

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

9. Morgan WA, Clayshulte BJ. Pecans lower low-density lipoprotein cholesterol in people with normal lipid levels. J Am Diet Assoc 2000;100:312-318.

10. Rajaram S, et al. A monounsaturated fatty acid-rich pecan-enriched diet favorably alters the serum lipid profile of healthy men and women. J Nutr 2001;131:2275-2279.

11. 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.

12. Kocyigit A, et al. Effects of pistachio nuts consumption on plasma lipid profile and oxidative status in healthy volunteers. Nutr Metab Cardiovasc Dis 2006;16:202-209. Epub 2006 Feb 9.

13. Alphan E, et al. Nutritional composition of hazelnuts and its effects on glucose and lipid metabolism. In: Kosal AI, et al, eds. Proceedings of the Fourth International Symposium on Hazelnut. Acta Hort 1997:305-310.

14. Mercanligil SM, et al. Effects of hazelnut-enriched diet on plasma cholesterol and lipoprotein profiles in hyper-cholesterolemic adult men. Eur J Clin Nutr 2006 Sep 13; Epub ahead of print.

15. Sabate J. Nut consumption and body weight. Am J Clin Nutr 2003;78(3Suppl):647S-650S.

16. Griel AE, et al. Improved diet quality with peanut consumption. J Am Coll Nutr 2004;23:660-668.

17. Wien MA, et al. Almonds vs complex carbohydrates in a weight reduction program. Int J Obes Relat Metab Disord 2003;27:1365-1372. Erratum in: Int J Obes Relat Metab Disord 2004;38:459.

18. Jenkins DJ, 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.

19. Jenkins DJ, et al. Direct comparison of a dietary port-folio of cholesterol-lowering foods with a statin in hypercholesterolemic participants. Am J Clin Nutr 2005;81:380-387.

20. Department of Health and Human Services and the Department of Agriculture. Dietary Guidelines for Americans. Bethesda, MD; 2005.

21. Clarke SD. Polyunsaturated fatty acid regulation of gene transcription: A molecular mechanism to improve the metabolic syndrome. J Nutr 2001;131:1129-1132.

22. Zhao G, et al. Anti-inflammatory effects of polyunsaturated fatty acids in THP-1 cells. Biochem Biophys Res Comm 2005;336:909-917.

23. National Cholesterol Education Program. 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. Bethesda, MD: National Heart, Lung, and Blood Institute, National Institutes of Health; 2002. NIH Publication No. 02-5215.

24. American Heart Association Nutrition Committee; Lichtenstein AH, et al. Diet and lifestyle recommendations revision 2006: A scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114:82-96. Epub 2006 Jun 19. Erratum in: Circulation 2006;114:e629; Circulation 2006;114:e27.

25. Bantle JP, et al. Nutrition recommendations and interventions for diabetes—2006: A position statement of the American Diabetes Association. Diabetes Care 2006;29:2140-2157.

26. Estruch R, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: A randomized trial. Ann Intern Med 2006;145:1-11.