Nuts Reduce Risk of Cardiovascular Disease
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 receives research support from Hershey Foods and the California Pistachio Commission.
Part 1 of a Series on Cardiovascular Disease
Numerous epidemiologic and clinical studies have demonstrated the potent cardioprotective benefits of nut consumption on multiple cardiovascular disease (CVD) risk factors, including both major and emerging risk factors.1-11 Results of epidemiologic studies have consistently shown that tree nut consumption decreases rates of coronary disease events, sudden cardiac death, diabetes, and gallstones. The clinical studies conducted to date have assessed the effects of different tree nuts, including walnuts, almonds, macadamia nuts, pecans, pistachios, and hazelnuts on lipids and lipoproteins, measures of vascular function, blood pressure, blood glucose levels, and markers of inflammation. Importantly, the effects have been shown in clinical studies that have employed a wide variety of study designs (self-selected, supplement studies, controlled feeding trials) in different populations, including men and women of all ages, African Americans, and persons with diabetes. In addition, mechanistic studies have been conducted that have provided insights about the underlying biological events that account for the specific cardioprotective effects of nut consumption.
Introduction
Nuts, a complex plant food, are low in saturated fatty acids (SFA) and are rich sources of unsaturated fat, predominantly monounsaturated fatty acids and omega-6 polyunsaturated fatty acids (PUFA). Some nuts provide omega-3 PUFA in smaller amounts. Walnuts are the richest nut source of the omega-3 PUFA α-linolenic acid (ALA), providing 9-10% of total fatty acids. Pecans and pine nuts provide 1% and 0.8% of ALA, respectively. Pistachios, macadamia nuts, and cashews provide 0.2.-0.3% of ALA. In addition, they also contain several nonfat constituents such as plant protein, fiber (including soluble fiber), micronutrients (e.g., copper and magnesium), plant sterols, and other phytochemical compounds.2 Because nuts have a favorable fatty acid profile and contain several bioactive compounds that may confer additional protective effects, there is interest in evaluating the role of nuts in lowering various risk factors for CVD and diabetes.
The unique nutrient profile and fiber content of nuts beneficially affect lipids and lipoproteins. Nuts are a source of dietary fiber, and soluble fiber has a blood cholesterol-lowering effect. Collectively, the fatty acid profile and fiber content of nuts can markedly lower LDL-cholesterol (LDL-C). In fact, the cholesterol reduction observed in clinical studies of nuts is about 25% greater than expected.10,12 In a recent review of clinical studies, 10 of 17 controlled feeding studies demonstrated a decrease in LDL-C that was greater than predicted using blood cholesterol-predictive equations.10 The predicted average decrease in LDL-C for these 17 studies was -0.23 mmol/L, with an observed decrease of -0.29 mmol/L when comparing the tree nut-rich diet to the control diet. It has been speculated that other nut constituents such as plant protein and possibly other factors (yet to be identified) could account for this effect.
Other nutrients in nuts that favorably affect lipids and lipoproteins are antioxidants, including vitamin E (including tocotrienols), other vitamins, and minerals such as folate, potassium, and magnesium, as well as non-nutrient bioactive compounds such as phytosterols and other phytochemical compounds including ellagic acid, flavonoids, phenolic compounds, and luteolin.2 Many of these could protect LDL-C against oxidative modification; others reduce cholesterol absorption and thereby decrease total cholesterol (TC) and LDL-C levels. Thus, the nutrient profile of nuts favorably affects lipid and lipoprotein CVD risk factors in a diversity of ways that reflects the portfolio of nutrients they contain.
Epidemiologic Studies
Results from epidemiologic studies clearly support the beneficial association between frequent nut consumption and lower risks of CVD. When Fraser et al analyzed the data from the Adventist Health Study (AHS), a prospective cohort investigation of 31,208 non-Hispanic white California Seventh-Day Adventists, the authors found that subjects who consumed nuts frequently (more than four times/week) experienced substantially fewer fatal coronary heart diseases (CHD) events (relative risk [RR] 0.52; 95% confidence interval [CI] 0.36-0.76) and nonfatal myocardial infarctions (MI) (RR 0.49; 95% CI 0.28-0.85), when compared with those who consumed nuts less than one time/week.5 These findings persisted after covariate adjustment. Compared with the group eating nuts less than one time/week, those who ate them 1-4 times/week had a 22% reduced risk of acute MI, whereas those eating nuts five or more times/week experienced a 51% reduction in risk. The data showed that 32% of the nuts consumed were peanuts (legumes or ground nuts), 29% were almonds, 16% were walnuts, and 23% were other kinds of nuts. The authors concluded that frequent nut consumption was protective for both fatal and nonfatal CHD events.
A later report from the same group showed that when compared to those with low intake of nuts, age of CHD onset in both genders was delayed by about four years among the AHS population consuming nuts more than five times/week.13 This was associated with a life expectancy free of CHD that was longer by 5.6 years and a CHD risk that was 12% lower.
In the Iowa Women's Health Study, which followed 34,500 postmenopausal women for five years, Ellsworth et al found that coronary mortality was inversely associated with nut intake.6 After adjustment for established ischemic heart disease (IHD) risk factors and energy intake, women who consumed more than one serving/week of nuts experienced a 40% reduction in IHD risk compared with those who ate nuts less frequently. A threshold effect seems to exist at a consumption frequency of less than one time/week. Consumption of nuts a few times per month conferred no appreciable benefit for IHD, but at a frequency of consumption of one or more times/week an inverse, graded relation was observed. It should be noted that only a relatively small percentage of this population consumed nuts frequently, which limited the statistical power.
Analysis of data from the Nurses' Health Study included 86,016 women aged 34-59 years without previously diagnosed CHD, stroke, or cancer at baseline in 1980.7 During 14 years of follow-up, 1,255 major coronary disease events occurred, including 861 cases of nonfatal MI and 394 cases of fatal CHD. After multivariate adjustment, compared with women who never ate nuts or who ate less than one unit/week (1 ounce), women who ate more than five units of nuts/week (5 ounces) had a significantly lower risk for total CHD (RR 0.65; 95% CI 0.47-0.89). The magnitude of risk reduction was significant and similar for both fatal CHD (RR 0.61; 95% CI 0.35-1.05) and nonfatal MI (RR 0.68; 95% CI 0.47-1.00).
Albert et al assessed data from 21,454 male participants enrolled in the Physicians' Health Study.4 Nut consumption was collected by an abbreviated food frequency questionnaire after 12 months of follow-up. During 17 years follow-up, 201 sudden deaths (176 definite and 25 probable) were documented. After adjustment for age, aspirin, and beta-carotene assignment, men who ate nuts more frequently (two ore more servings/week) tended to have a lower risk of sudden cardiac death (RR 0.64; 95% CI 0.40-1.01; P for trend 0.04). After multivariate adjustment, compared with men who consumed nuts less than one serving/month, the RR of those who consumed two or more servings/week was 0.53 (95% CI 0.30-0.92; P for trend 0.01) for sudden cardiac death and 0.70 (95% CI 0.50-0.98; P for trend 0.06) for total CHD death. The relationship between nut consumption and sudden cardiac death appeared linear. In contrast to the inverse relationship with sudden cardiac death, nut consumption was not significantly associated with risk of nonsudden CHD death or nonfatal MI. Risk reduction was apparent only in the highest intake category (two or more servings/week). The men in the highest category had a 30% reduction in risk of CHD death compared with those who rarely or never consumed nuts.
Data from the Nurses' Health Study were also used to examine the relationship between nut consumption and the risk of Type 2 diabetes. In this prospective cohort study of 83,818 women aged 34-59 years, nut consumption was inversely associated with risk of Type 2 diabetes after adjustment for age, body mass index (BMI), family history of diabetes, physical activity, smoking, alcohol use, and total energy intake.11 Compared to individuals who "never/almost never" consumed nuts, those who consumed nuts five or more times/week had a multivariate RR of 0.73 (95% CI 0.60-0.89; P for trend < 0.001) for the development of Type 2 diabetes. When further adjustments were made for intakes of dietary fats, cereal fiber, and other dietary factors, the results did not change. The inverse association between nut consumption and the risk of Type 2 diabetes also persisted within strata defined by levels of BMI, smoking, alcohol use, and other diabetes risk factors.
Nut consumption also has been shown to reduce risk of gallstone disease in men and women. With 457,305 person-years of follow-up in the Health Professionals Follow-up Study, 1,833 participants reported gallstone disease.14 After multivariate adjustment, men consuming nuts five or more times/week had a significantly lower risk of gallstone disease (RR = 0.70; 95% CI 0.60-0.86; P for trend < 0.001) than did men who never ate nuts or who ate nuts less than one time/month. Further adjustment for fat consumption (saturated fat, trans fat, polyunsaturated fat, and monounsaturated fat) did not materially alter the relation.
Results of the Nurses' Health Study showed a similar relationship between nut consumption and risk of gallstone disease in women.15 In a cohort of 80,718 women aged 30-55 years, those who consumed 5 ounces or more of nuts/week had a significantly lower risk of gallstones (RR = 0.75; 95% CI 0.66-0.85; P for trend < 0.0001) than did women who never ate nuts or who ate less than 1 ounce/month. Again, further adjustment for fat consumption did not change the results.
In summary, the epidemiologic evidence consistently indicates that 4-5 servings of nuts per week reduce the risk of CVD from 35% to 50%. In addition, nut consumption has been shown to reduce risk of Type 2 diabetes in women and risk of gallstones in men and women.
Clinical Nutrition Studies
Numerous clinical studies have shown consistently that a nut/nut oil-containing diet low in saturated fat and cholesterol beneficially affects lipids and lipoproteins vs. a control diet (typically either a low-fat diet or an average American/Western diet). Oxidative stress is a key event in atherogenesis, and many studies also have evaluated the effect of nut consumption on LDL oxidation. As will become evident below with regard to walnuts (and continuing in Part 2 of this series with almonds, macadamia nuts, pecans, pistachios, and hazelnuts), there is an impressive database showing that tree nut consumption improves the lipid CHD risk factor profile, which may explain the cardioprotective effects of nut consumption that have been demonstrated in the epidemiologic studies.
Walnuts
Walnuts have been studied extensively for their effects on blood lipids and lipoproteins, endothelial health, and the reduction of risk factors for Type 2 diabetes. While most nuts are rich in monounsaturated fatty acids (MUFA), walnuts are unique in that they contain high levels of polyunsaturated fatty acids (PUFA), including both linoleic acid (LA) and ALA.16 Walnuts also are high in several cardioprotective nutrients including fiber, vitamin E, folate, and potassium. Studies evaluating the effects of walnuts on risk factors for CVD and Type 2 diabetes have been conducted in both controlled feeding and self-selected diet settings in healthy individuals and those at risk for chronic disease.
Six studies evaluated the effects of walnut supplementation on blood lipids and lipoproteins in both a self-selected diet and a controlled feeding setting.17-24 In a free-living, two-period randomized crossover study, researchers evaluated whether a 78 g/d supplement of walnuts (20% of the total energy in the supplemented diet; 55% of the total fat [38%] in the diet) would have added effects on the reduction of blood lipids beyond that of a fat-modified, low-fat (30% total fat) diet.17 LDL-C (-8%), TC (-4%), and apolipoprotein B (-13%) were significantly lower (P < 0.01) following the walnut-supplemented diet compared to baseline. Following the fat-modified diet, LDL-C (-5%), TC (-2%), and apolipoprotein B (-8%) were also reduced; however, these results did not differ significantly from baseline levels. Increases in HDL-cholesterol (HDL-C) following the fat-modified (11%) and walnut-supplemented (14%) diets were both significantly different from baseline levels, although not different from one another.
When testing the effects of walnut supplementation in the controlled feeding setting, the supplementation of 48 g of walnuts per 2,020 kcal to a low-fat, low-saturated fat (34% total fat, 8% SFA, 12% MUFA, and 17% PUFA) diet resulted in significant reductions (P < 0.01) in both TC (8%) and LDL-C (12%), and non-significant changes in triglycerides (-1%) and HDL-C (+2%).18 When the same amount of walnuts was supplemented in a habitual diet (37% total fat, 10% SFA, 13% MUFA, and 16% PUFA), there were minimal changes in the lipid and lipoprotein profile (3% reduction in total cholesterol, 10% reduction in triglycerides, 2% increase in LDL-C, 10% decrease in HDL-C). The HDL-C response to walnut supplementation was the only significant effect (P < 0.01).
In addition to the standard lipid and lipoprotein profiles, the investigators also measured lipoprotein subclasses and particle sizes. Small, dense LDL particles increase risk of CVD.19 These smaller LDL particles are formed primarily in response to an elevation in triglycerides. Walnut supplementation has been shown to preferentially lower small, dense LDL particles.18 The addition of walnuts to the habitual diet decreased the number of small dense LDL from 46% on the habitual diet to 33% with walnut supplementation (P < 0.01). However, addition of walnuts to the fat-modified, low-fat diet did not affect LDL particle size. These results indicate that walnut supplementation to an average American diet, but perhaps not a fat-modified, low-fat diet, may create a favorable shift in the distribution of LDL particle size even when of LDL-C levels remain unchanged.
A randomized, three-period crossover design was used to evaluate the effects of two walnut-rich diets on risk factors for CVD in hypercholesterolemic men and women.20 Walnuts and walnut oil represented one-half of the total fat in the two high-PUFA diets (LA and ALA). The daily consumption of walnuts and walnut oil was 37 g and 15 g, respectively, for a diet that provided 2,400 kcal/d. Flaxseed oil, ~20 g/d for an energy intake of 2,400 kcal/d, also was used to increase the ALA content of the ALA diet. Compared with the control diet (an average American diet [AAD]), the two high-PUFA diets elicited similar lipid-lowering responses. Serum TC, LDL-C, and triglycerides were 10.9%, 12.3%, and 18.4% lower, respectively, following the consumption of the LA diet (P < 0.05), and were 10.8%, 11.0%, and 18.4% lower, respectively, when comparing the ALA diet to the AAD (P < 0.05). Although the decrease in HDL-C following the ALA diet was significantly different compared to the AAD (P < 0.05), there were no differences in HDL-C response between the LA and ALA diets; the two high-PUFA diets reduced the ratio of TC:HDL-C similarly. Similar improvements in the lipid and lipoprotein profile have been observed with the incorporation of 44-58 g/d of walnuts into a low-fat (25% total fat) diet,21 the inclusion of 41-56 g/d of walnuts in a Mediterranean diet,22 and the incorporation of 64 g/d of walnuts into a low-fat cholesterol-lowering diet (39% total fat).23 Even greater improvements have been observed with the incorporation of 84 g of walnuts per 2,500 kcal to a Step 1 diet.24 In the study by Sabate et al, when walnuts provided 20% of total calories, LDL-C was decreased by 16%.
In addition to the observed benefits on lipids and lipoproteins, walnuts have also been shown to reduce the risk of CVD by favorably modulating other risk factors, such as endothelial function. Ros and colleagues tested the hypothesis that walnuts would decrease cholesterol levels and also favorably affect endothelial function in individuals with hypercholesterolemia.25 Endothelial dysfunction is associated with atherosclerosis and the development of cardiovascular disease. Because nuts proportionally contain a large amount of arginine, the precursor of the endogenous vasodilator nitric oxide, nuts may affect cardiovascular health via an improvement in endothelial function. In a two-period randomized crossover feeding study, 21 hypercholesterolemic men and women consumed a Mediterranean-type cholesterol-lowering diet and a walnut-enriched diet, both of which contained 33% of calories from total fat. Following the consumption of the walnut-enriched diet there were significant reductions in TC (-4.4%; P < 0.05) and LDL-C (-6.4%; P = 0.01) compared to the Mediterranean diet. The walnut-enriched diet also led to a 64% increase in endothelium-dependent vasodilation. Moreover, another study demonstrated a beneficial effect of a high-fat meal (80 g) with walnuts (40 g) compared with olive oil (25 g) on postprandial vasoreactivity.26 Adding walnuts acutely to a high-fat meal improved flow-mediated dilation, which typically decreases in response to a fat load. The results of these studies demonstrate the benefits of walnut consumption beyond that of their lipid-lowering effects.
References
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19. Austin MA, et al. Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk. Circulation 1990;82:495-506.
20. Zhao G, et al. Dietary alpha-linolenic acid reduces inflammatory and lipid cardiovascular risk factors in hypercholesterolemic men and women. J Nutr 2004;134:2991-2997.
21. Iwamoto M. Serum lipid profiles in Japanese women and men during consumption of walnuts. Eur J Clin Nutr 2002;56:629-637.
22. Zambon D, et al. Substituting walnuts for monounsaturated fat improves the serum lipid profile of hypercholesterolemic men and women. A randomized crossover trial. Ann Intern Med 2000;132:538-546.
23. Morgan JM, et al. Effects of walnut consumption as part of a low-fat, low-cholesterol diet on serum cardiovascular risk factors. Int J Vitam Nutr Res 2002;72:341-347.
24. Sabate J, et al. Effects of walnuts on serum lipid levels blood pressure in normal men. N Engl J Med 1993;328:603-607.
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26. Cortes B, et al. Acute effects of high-fat meals enriched with walnuts or olive oil on postprandial endothelial function. J Am Coll Cardiol 2006;48:1666-1671. Epub 2006 Sep 26.
Griel A, Kris-Etherton P. Nuts reduce risk of cardiovascular disease. Altern Med Alert 2007;10(2):17-21.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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