The Mediterranean Diet: An Evidence-Based Approach

The Mediterranean Diet An Evidence-Based Approach

Edited by Victor R. Preedy King’s College London, London, UK

Ronald Ross Watson University of Arizona, Tucson, AZ, USA

AMSTERDAM • BOSTON • HEIDELBERG • LONDON NEW YORK • OXFORD • PARIS • SAN DIEGO SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO Academic Press is an imprint of Elsevier

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4 3 2 1

Chapter 17

Contribution of Nuts to the Mediterranean Diet Emilio Ros, MD, PhD1,2 1 2

Lipid Clinic, Endocrinology & Nutrition Service, Institut d’Invesigacions Biome`diques, August Pi Sunyer, Hospital Clinic, Barcelona, Spain. CIBER Fisiopatologia de la Obesidad y Nutricioń (CIBERobn), Instituto de Salud Carlos III (ISCIII), Barcelona, Spain.

ABBREVIATIONS ALA CHD MUFA NO PREDIMED PUFA RCT SFA

a-linolenic acid coronary heart disease monounsaturated fatty acids nitric oxide PREvencioń con DIeta MEDiterrańea polyunsaturated fatty acids randomized clinical trial saturated fatty acids

INTRODUCTION By definition, tree nuts are dry fruits with one seed in which the ovary wall becomes hard at maturity. Common edible tree nuts include almonds, Brazil nuts, cashews, hazelnuts, macadamias, pecans, pine nuts, pistachios, and walnuts, but the consumer definition also includes peanuts, which botanically are legumes but have a nutrient profile similar to tree nuts are thus identified as part of the nuts food group [1]. Chestnuts are tree nuts as well, but they are different from all other common nuts because of being starchier and having a different nutrient profile. For the purpose of this chapter, the term nuts comprises all common tree nuts (with the exception of chestnuts) plus peanuts. Extensive research on nuts and health outcomes has been conducted during the 20 years since the publication of the results from the pioneering Adventist Health Study, relating nut consumption to a lower risk of coronary heart disease (CHD) in 1992 [2]. That soon was followed by a landmark randomized clinical trial (RCT) by Sabate´ et al. [3], showing an association of walnut intake with reduction of serum cholesterol levels. Nuts, seeds, and pulses are all nutrient-dense foods and have been a regular constituent of mankind’s diet since preagricultural times [4]. In the past century, however, nut consumption in most industrialized nations followed a downward trend, becoming only a marginal source of energy in the daily diet, except for vegetarians and other health-conscious populations such as Seventh Day Adventists [5]. Nevertheless, there has been a recent upsurge of nut intake in Western countries following both the inclusion of this food group in many guidelines for healthful eating and wide media advertisement of accruing evidence of their beneficial health effects. Thus, leading experts in nutritional epidemiology have proposed nuts as a component of optimal diets for the prevention of CHD [6]. Furthermore, in the summer of 2003, the US Food and Drug Administration issued a health claim for nuts and nut-containing products because of the link of nut consumption with a reduced risk of heart disease [7]. Nuts were included in the American Heart Association report setting goals for health promotion and disease reduction for 2020 [8] and are an integral part of the plant-based dietary patterns recommended by dietary guidelines [9]. The scientific evidence behind the proposal of nuts as heart-healthy foods stem from both epidemiological observations suggesting the frequency of nut intake relates inversely to incident CHD and diabetes and from numerous RCTs showing beneficial effects of nut intake on blood lipids and other intermediate markers of CHD [9,10]. The mechanism for these salutary effects probably lies in the interaction of the many bioactive constituents of nuts, which may all favorably influence human physiology. Thus, nuts contain large amounts of vegetable protein and fat, which is made up mostly of unsaturated fatty acids; The Mediterranean Diet © 2015 Elsevier Inc. All rights reserved.

175

176 SECTION 2 Components of the Mediterranean Diet

they are also dense in dietary fiber; vitamins (e.g., folic acid, niacin, tocopherols, vitamin B6); minerals (e.g., calcium, magnesium, potassium, zinc); and many other bioactive constituents such as phytosterols and phenolic compounds [1]. Contrary to expectations because of the high energy content of nuts, epidemiological studies and clinical trials suggest that their regular consumption is unlikely to promote weight gain [11]. This chapter summarizes current knowledge on the expanding topic of nuts and health and on their contribution to the healthful properties of the Mediterranean diet.

NUTS IN THE MEDITERRANEAN DIET The oldest evidence of cultivation of the common tree nuts almonds (Prunus amygdalus), hazelnuts (Corylus avellana), walnuts (Juglans regia), and pistachios (Pistachia vera) are from Asia, mainly the Anatolian peninsula (modern Turkey). From there, cultivars of these trees were introduced in Greece, then in Italy during the Roman Empire, and extended to all of Europe during the Middle Ages [12]. Common pine nuts (Pinus pinea) are not usually collected from plantations but from natural forests, mostly in the Mediterranean area. The most popular edible tree nuts are precisely the Asian/Mediterranean nuts: almonds, walnuts, hazelnuts, and pistachios. In Europe, where comparisons across different countries have been made, nut supply is reported to be highest for Mediterranean countries [13]. In the European Prospective Investigation into Cancer and Nutrition, wherein 24-h food records were collected for nearly 37,000 subjects from 10 countries [14], a clear north-to-south gradient was apparent; Swedish individuals had a mean whole nut and peanut intake of 0.61 g/day and average portion size of 15.1 g/day, whereas Spanish subjects had a mean intake of 4.83 g/day and average portion size 34.7 g/day. Of note, the proportion of subjects reporting nut consumption on the day of the 24-h food recall followed a similar pattern (Sweden 2.5% and Spain 11.9%). Thus, nuts are an important component and part of the definition of the Mediterranean diet, the traditional dietary pattern found in Crete, Greece, Italy, and Spain in the early 1960s. This dietary pattern is characterized by a high intake of cereals, vegetables, fruits, nuts, and olive oil; a moderate intake of fish and alcohol (mostly wine); and a low intake of dairy products, red meat and meat products, and sweets [15]. Nuts are incorporated in the Mediterranean diet in various ways: they are consumed as snacks, desserts, or part of a meal or are eaten whole (fresh or roasted), in spreads (almond paste), as oils, or hidden in commercial products, mixed dishes, sauces, pastries, ice creams, and baked goods. Almond-based desserts, such as nougat and marzipan, are customary in many Mediterranean areas for almost ritual consumption during holiday seasons such as Christmas. In the past decade there has been a slowly increasing pattern of nut consumption in both Mediterranean areas and Western countries, likely reflecting increased awareness of the health-promoting properties of nuts and their lack of fattening power.

NUTRIENT CONTENT OF MEDITERRANEAN NUTS As mentioned, nuts are nutrient-dense foods. With the exception of chestnuts, which contain little fat, nuts have a high total fat content, ranging from 46% in pistachios to 68% in pine nuts, and they provide 23 to 27 kJ/g (Table 1). Thus, nuts are one of the natural plant foods richest in fat after vegetable oils. However, the fatty acid composition of nuts is beneficial because the saturated fatty acid content is low (range, 4–6%), and nearly one-half of the total fat content is made up of unsaturated fat, monounsaturated fatty acids (MUFAs) in most nuts, a predominance of polyunsaturated fatty acids (PUFAs) over MUFAs in pine nuts, and mostly PUFAs, both linoleic acid and a-linolenic acid (ALA), the plant omega 3 fatty acid, in walnuts [1]. With regard to walnuts, it must be noted that of all edible plants they are the whole food with the highest content in ALA. As discussed below, the particular lipid profile of nuts in general and walnuts in particular is likely to be an important contributor to the beneficial health effects of frequent nut consumption. Nuts are also rich sources of other bioactive macronutrients that have the potential to beneficially affect metabolic and cardiovascular outcomes. They are an excellent source of protein (25% of energy) and often have a high content of the amino acid L-arginine, which is the substrate for endothelium-derived nitric oxide synthesis, a principal regulator of vascular tone and blood pressure [16]. This explains why nut intake might help improve vascular reactivity, as discussed below in the section “Nut Consumption and Health Outcomes” subheading “Randomized Clinical Trials.” Nuts also are a good source of dietary fiber, which ranges from 4 to 11/100 g nuts (Table 1), and standard servings provides 5–10% of daily fiber requirements [1]. Among the constituents of nuts are significant amounts of essential micronutrients that are associated with an improved health status when consumed at doses beyond those necessary to prevent deficiency states. Mediterranean nuts contain sizeable amounts of the B vitamin folate (Table 2). They are also rich sources of antioxidant vitamins (e.g., tocopherols) and polyphenols, necessary to protect the germ from oxidative stress and preserve the reproductive potential of the seed but also bioavailable after consumption and capable of providing a significant antioxidant load [17]. Almonds in particular are especially

Contribution of Nuts to the Mediterranean Diet Chapter 17

177

TABLE 1 Average Nutrient Composition of Mediterranean Nuts (Per 100 g) Nuts

Energy (kJ)

Protein (g)

Fiber (g)

Fat (g)

SFAs (g)

MUFAs (g)

PUFAs (g)

LA (g)

ALA (g)

Almonds

2418

21.3

8.8

50.6

3.9

32.2

12.2

12.2

0.00

Hazelnuts

2629

15.0

10.4

60.8

4.5

45.7

7.9

7.8

0.09

Pine nuts

2816

13.7

3.7

68.4

4.9

18.8

34.1

33.2

0.16

Pistachios

2332

20.6

9.0

44.4

5.4

23.3

13.5

13.2

0.25

Walnuts

2738

15.2

6.4

65.2

6.1

8.9

47.2

38.1

9.08

Data are for raw nuts. SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; LA, linoleic acid; ALA, a-linolenic acid. Source: US Department of Agriculture Nutrient Data Base at: http://www.nal.usda.gov/fnic/cgi-bin/nut_search.pl [accessed 20.09.12].

TABLE 2 Average Composition of Mediterranean Nuts in Selected Micronutrients, Minerals and Phytochemicals (Per 100 g) Nuts

Folate (mg)

a-Tocopherol (mg)

Potassium (mg)

Magnesium (mg)

Calcium (mg)

Phytosterols (mg)

Polyphenols (mg)

Almonds

29

25.9

728

275

248

120

287

Hazelnuts

113

15.0

680

163

114

96

687

Pine nuts

34

9.3

597

251

16

141

58

Pistachios

51

2.3

1025

121

107

214

1420

Walnuts

98

0.7

441

158

98

72

1576

Data are for raw nuts. Sources: US Department of Agriculture Nutrient Data Base at: http://ndb.nal.usda.gov/ndb/foods/list [accessed 20.09.12]; National Institute for Health and Welfare, N.U. Fineli. Finnish Food Composition Database at: http://www.fineli.fi [accessed 26.09.12]; and Phenol-Explorer 2.0. Data base on polyphenol content in foods at: http://www.phenol-explorer.eu [accessed 25.09.12].

rich in a-tocopherol, whereas walnuts contain significant amounts of its isomer g-tocopherol, which has been investigated much less than a-tocopherol but is increasingly recognized as a relevant antiatherogenic molecule [18]. Remarkably, most of the antioxidants in all nuts are located in the pellicle or outer soft shell, as shown for almonds [19], and 50% or more of them are lost when nuts are peeled or roasted [17]. These facts, usually overlooked in prior studies of nuts, should be considered when giving advice on nut consumption in healthful diets. Walnuts are an exception because they are almost always consumed as the raw, unpeeled product; moreover, among nuts, walnuts have the highest polyphenol content [20]. Nuts are cholesterol free, but their fatty fraction contains sizeable amounts of chemically related noncholesterol sterols belonging to a heterogeneous group of compounds known as plant sterols or phytosterols [1] (Table 2), which are non-nutritive components of all plants that play an important structural role in plant membranes, where they serve to stabilize phospholipid bilayers, just as cholesterol does in animal cell membranes [21]. Phytosterols interfere with cholesterol absorption and thus help lower blood cholesterol when present in gram doses in the intestinal lumen. The mechanism of action of phytosterols has been linked to their hydrophobicity, which is higher than cholesterol because of a bulkier hydrocarbon molecule and entails a higher affinity for micelles than has cholesterol. Consequently, cholesterol is displaced from micelles and the amount available for absorption is limited [22]. The phytosterol content of nuts very likely contributes to their cholesterol-lowering effect (see “Nut Consumption and Health Outcomes” subheading “Randomized Clinical Trials”). Compared to other commonly consumed foods, nuts have an optimal nutritional density regarding beneficial minerals such as calcium, magnesium, and potassium (Table 2). Like that of most vegetables, the sodium content of nuts is very low. A high intake of calcium, magnesium, and potassium, together with a low sodium intake, is associated with protection against hypertension, insulin resistance, and overall cardiovascular risk [23], as well as bone demineralization.


↓ Cholesterol

Unsaturated fatty acids Phytosterols

Fiber

↓ Oxidation ↓ Inflammation

↑ Glucose control

Minerals (K, Mg, Ca) Tocopherols

Vegetable protein (L-arginine) Polyphenols

↑ NO ↓ Blood pressure ↑ FMD

↓ CVD and diabetes

FIGURE 1 Potential mechanisms of cardiometabolic protection by nut constituents. The consumption of nuts ameliorates cardiovascular health because of their unique composition, including bioactive nutrients and phytochemicals, which synergize to beneficially affect cardiometabolic pathways. The main known nutrients of nuts are represented, together with their principal biological targets (thin arrows). The net effects of nuts on intermediate markers of cardiovascular risk that have been demonstrated in clinical trials are lowered cholesterol, improved glycemic control, decreased blood pressure, improved vasomotion, and antioxidant and anti-inflammatory actions. The overall result is reduced cardiovascular disease and/or type 2 diabetes (thick arrows), as suggested in prospective cohort studies and observed in the PREDIMED trial. See text for details. K, potassium; Mg, magnesium; Ca, calcium; NO, nitric oxide; FMD, flow-mediated vasodilation; CVD, cardiovascular disease.

In summary, the macronutrient, micronutrient, and phytochemical components of nuts have all been documented to contribute to a reduced risk of CHD and related metabolic disturbances. As shown in Figure 1, most bioactive nut components synergize to affect multiple metabolic and vascular physiology pathways, leading to protection from cardiovascular disease and type 2 diabetes. For these reasons, whole, raw, unpeeled, and otherwise unprocessed nuts may be considered natural health capsules, where the whole is always better than the parts.

NUT CONSUMPTION AND HEALTH OUTCOMES Nut consumption has been and still is the focus of intense epidemiological and clinical research. Prospective studies have examined clinical cardiovascular end points, e.g., CHD, type 2 diabetes, stroke, heart failure, hypertension, and obesity, whereas RCTs have generally explored intermediate biomarkers of cardiovascular disease risk. An exception is the PREvencioń con DIeta MEDiterrańea (PREDIMED) trial of primary cardiovascular prevention, which includes nut supplementation in one study arm and has hard cardiovascular end points as the main study outcome [24]. The scientific evidence acquired from these studies is summarized below.

Epidemiological Studies As reviewed by Ros et al. [10], four large prospective studies examining associations of dietary components with health outcomes in the United States reported a beneficial effect of nut consumption on fatal and nonfatal CHD after follow-up of large cohorts of healthy subjects ranging from 6 to 18 years old (Figure 2). A pooled analysis of these studies indicated that subjects in the highest category of nut and/or peanut butter intake had a 37% reduction in multivariable-adjusted risk of fatal CHD [24]. A dose-response relationship between nut consumption and reduced CHD mortality was observed in all studies. The dose–response relationship between nut consumption and CHD risk resulted in an average 8.3% reduction for each weekly serving of nuts [25]. The consistency of findings in all studies points to a causal association between nut consumption and reduced CHD and suggests that nuts are probably one of the most heart-healthy foods in the usual diet. Findings from the Nurses’ Health Study suggested that nut and peanut butter consumption was associated with a reduced incidence of type 2 diabetes in women [26]. A subsequent report from a Chinese cohort of nearly 64,000 women also suggested a protective effect of nuts against diabetes risk [27]. These findings, however, were not confirmed in male participants in the Physicians’ Health Study [28]. Figure 3 illustrates the findings of the main prospective studies relating nut consumption to diabetes risk. Thus, regular consumption of nuts is clearly beneficial for CHD risk, but confirmation of any protective role against diabetes risk must await further studies. Additional reports from the Physicians’ Health Study showed no association between the frequency of nut intake and ischemic stroke [29] or heart failure [30]. While epidemiologic data on the relationship between nut consumption and


1.2

Relative risk (adjusted)

FIGURE 2 Incidence of fatal coronary heart disease by frequency of nut intake. The graph presents the results of four large prospective studies, all conducted in the United States, of nut consumption and risk of death from coronary heart disease.

179

1.0 Adventists Health Study 1992

0.8

Iowa Women’s Health Study 1993 Nurses’ Health Study 1998

0.6

Physicians’ Health Study 2002

0.4 0.2 0

1-2/mo

3-4/mo

1-4/wk

>5/wk

Frequency of nut intake

1.2

Relative risk (adjusted)

FIGURE 3 Incidence of type 2 diabetes by frequency of nut intake. Results of three large prospective studies of nut consumption and risk of diabetes. The two US studies considered the frequency of consumption of all nuts, including peanuts, whereas the Chinese study considered exclusively quintiles of peanut consumption.

1.0 Nurses’ Health Study 2002 Shanghai Women’s Health Study 2008 Physicians’ Health Study 2009

0.8

0.6

0.4

0.2 150 mg/dL, in whom a significant 10.2-mg/dL reduction was observed. A separate meta-analysis of 13 RCTs examined the effect of walnut-enriched diets on blood lipid levels [32]. Compared with control diets, diets containing walnuts in amounts varying from 30 to 108 g/day (10–24% of energy) were associated with weighted mean reductions of total cholesterol and LDL-cholesterol of 10.3 and 9.2 mg/dL, respectively (P < 0.001 for both), which concur with the results of the pooled analysis for different types of nuts [31]. Acute feeding studies indicate that nuts reduce postprandial glucose responses when consumed with foods that have a high glycemic index, suggesting that they may be useful in diabetic control [33]. Even though it seems counterintuitive to recommend an energy-dense food such as nuts to people with diabetes, it is important to underline that there is no evidence that their frequent consumption is associated with increased adiposity, as shown in a recent meta-analysis of RCTs using nut diets versus control diets [34]. Indeed, the common perception that fatty foods provide excess energy and thus promote obesity has had a negative effect on the image of nuts. The question of whether increasing the intake of nuts and therefore calories could lead to unwanted weight gain and related health problems, such as diabetes, is a critical one. Mechanistically, the lack of weight gain after consuming nuts is largely attributable to their prominent satiating effect, which results in food compensation accounting for up to 75% of the energy they provide [35]. An additional factor contributing to offset energy acquisition after eating nuts is fat malabsorption, documented as increased fecal fat excretion, which may be due in part to the high fiber content of nuts or to incomplete digestion of their matrices—the fat of nuts is enclosed within cell membranes, which are not readily available to digestive enzymes even after thorough mastication [36]. By virtue of their unique composition, nuts are likely to affect cardiometabolic markers other than blood lipids and glycemic control. Thus, studies have examined the effects of nuts on oxidative stress, inflammation, and vascular reactivity, as reviewed by Ros et al. [10,11]. Limited evidence from small RCTs suggests that nuts, particularly walnuts, have beneficial effects on blood pressure and endothelial function, which is attributable to their richness in L-arginine, PUFAs, and polyphenols [37]. Regarding oxidative stress, it is well known that PUFAs are more susceptible to oxidation than MUFAs [38], but nuts are a rich source of antioxidants. Available evidence suggests that MUFA-rich nuts (almonds, hazelnuts, pistachios) can moderately improve oxidative status, whereas PUFA-rich nuts (walnuts) have a neutral or slightly beneficial effect [39]. In any case, there is no evidence that frequent nut consumption reduces antioxidant defenses. Finally, nut feeding studies have documented reduced circulating concentrations of inflammatory cytokines but no consistent changes in C-reactive protein [11]. In summary, the emerging picture is that frequent nut consumption has beneficial effects on cardiovascular risk factors beyond well-established cholesterol lowering effects without incurring any undue increase in body weight.

Health Effects of Mediterranean Nuts in the PREDIMED Trial The PREDIMED study is a large, parallel group, multicenter, controlled, 5-year RCT conducted in Spain. Eligible participants were men 55 to 80 years of age and women 60 to 80 years of age who were at high risk for but had no cardiovascular disease at enrolment. Candidates for the study had to fulfill at least one of two criteria: type 2 diabetes or three or more cardiovascular risk factors, including current smoking, hypertension, hypercholesterolemia, low HDL-cholesterol, body mass index 25 kg/m2, or family history of premature CHD. Participants were randomized to three groups: two Mediterranean diets supplemented with either extra virgin olive oil or mixed nuts or a control diet (advice on a low-fat diet). They received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra virgin olive oil (1 L/week), mixed Mediterranean nuts (30 g/day; 15 g walnuts, 7.5 g almonds, and 7.5 g hazelnuts), or small nonfood gifts. Of note, the diets were ad libitum and increased physical activity was not promoted; thus the full effect of dietary intervention by itself, without decreased energy intake or increased energy expenditure, could be ascertained. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or cardiovascular death). The detailed protocol has been published elsewhere [24]. Since its inception in October 2003, the trial has provided a continuous flow of data on the beneficial health effects of Mediterranean diets enriched with both supplemental foods, culminating with the recent publication of results on the main cardiovascular outcome [40]. The results have generally been similar


181

for both the extra virgin olive oil- and nut-supplemented Mediterranean diets in comparison with the control diet. The principal results concerning the Mediterranean diet enriched with nuts are summarized below. Results of a pilot study involving the first 772 participants completing the intervention for 3 months [41] showed that, compared with the control diet, the two enhanced Mediterranean diets resulted in significant reductions of both systolic and diastolic blood pressure and total and LDL-cholesterol; increased HDL-cholesterol; decreased fasting glucose levels in diabetic participants and increased insulin sensitivity in those without diabetes; and reduction in circulating levels of inflammatory cytokines. Furthermore, the nut-enriched diet also reduced fasting triglyceride levels [41]. While most results confirmed prior data, the blood pressure-lowering effect of the nut diet was novel. Another PREDIMED report provides insight into the possible mechanism by showing that both the nut- and olive oil-enriched diets were associated with reduced cholesterol-to-phospholipid ratios of erythrocyte membranes, which would translate into increasing membrane fluidity [42]. Another report from the 3-month pilot study showed that both supplemented Mediterranean diets were associated with reduced oxidized LDL levels [43], which support the beneficial effects of nut diets on oxidative stress. A further substudy analyzed 3-month changes in both circulating inflammatory biomarkers and in the expression of ligands for inflammatory molecules in circulating monocytes after the study diets [44]. The findings indicate reductions in both circulating inflammatory mediators and, importantly, reduced monocyte expression of proinflammatory ligands after both extra virgin olive oil- and nut-enriched Mediterranean diets, thus beginning to unravel the molecular bases for the anti-inflammatory effects of nut consumption. Regarding cardiometabolic outcomes, the PREDIMED trial has provided first-level evidence for the protection afforded by long-term consumption of Mediterranean nuts in the context of a healthful diet against metabolic syndrome [45], type 2 diabetes [46], and cardiovascular diseases [40]. In the first 1224 trial participants completing the intervention for 1 year, the nut-enriched Mediterranean diet was associated with a 14% reduction in the prevalence of metabolic syndrome, which was mainly due to reduced visceral adiposity [45]. Because there were no weight changes, this suggests fat redistribution away from the abdominal compartment. In one of the 11 PREDIMED recruiting centers, oral glucose tolerance tests were performed yearly in nondiabetic participants to accurately detect incident diabetes. Results of this substudy of 418 subjects followed for a mean of 4 years showed that both enhanced Mediterranean diets protected against development of diabetes, and the reduction of incident diabetes in the nuts arm was 52% compared with the control diet [46]. Again, this beneficial effect took place in the absence of weight loss or increased energy expenditure during physical activity. The final results of the PREDIMED trial have recently been published, showing for the first time a reduction of incident cardiovascular diseases after long-term consumption of a diet enriched by nuts [40]. After a median follow-up of 4.8 years in 7447 participants, those assigned the two Mediterranean diets showed a 30% reduction in cardiovascular disease events (myocardial infarction, stroke, or cardiovascular death) compared with the control diet. The nut diet also was associated with a significant 49% reduction in stroke risk. No effects of the intervention diets could be discerned on myocardial infarction alone or total mortality. Of note, the interventions were intended to improve the overall dietary pattern, but the major between-group differences in food intake were for the supplemental items. Thus, nuts were probably responsible for most of the observed benefits in the Mediterranean diet with nuts group. The results of the PREDIMED trial show the full potential of nuts and other healthy foods, such as extra virgin olive oil, to improve cardiovascular health.

CONCLUSION Nuts are energy-dense foods rich in bioactive macronutrients, micronutrients, and phytochemicals. The unique composition of nuts is critical to their health effects. Indeed, there is consistent evidence from epidemiologic and clinical studies of the beneficial effects of nut consumption and their constituents on cardiovascular risk, as well as on diabetes and major and emerging cardiovascular risk factors, as summarized in Table 3. The evidence to-date that including nuts in a healthy dietary pattern affords protection against cardiometabolic disorders beyond that attributable to the other components of the diet is convincing. Importantly, these effects take place without undue weight gain, or even with reduced adiposity, and target multiple cardiovascular risk factors and mechanisms, which help explain why nuts so potently reduce cardiovascular risk. The PREDIMED trial has already demonstrated that long-term adherence to a healthful diet enriched with one daily serving of Mediterranean nuts reduces the incidence of type 2 diabetes and cardiovascular disease, particularly stroke. Ongoing research within this landmark trial will eventually prove whether the beneficial properties of nuts extend to the prevention of other prevalent chronic diseases, including cancer, heart failure, and neurodegenerative disorders.


TABLE 3 Effects of Nut Consumption on Cardiovascular Diseases and Risk Factors: Summary of the Scientific Evidence Disease/Factor

Effect

Level of Evidence

Coronary heart disease

Decrease

++

Ischemic stroke

No change

+

Heart failure

No change

+

Hypertension

Decrease

Diabetes

No change/decrease

Inflammatory markers

Decrease

+

Body weight

No change/decrease

++

Decreasea

++

a

++

Epidemiologic studies

Clinical studies Blood lipid profile Total cholesterol LDL-cholesterol HDL-cholesterol Triglycerides Insulin sensitivity

Decrease a

+

Increase

Decrease

a

a

+ +

Increase

Decrease

a

+

Oxidation

Decrease

a

+

Inflammation

Decrease

+

Vascular reactivity

Increase

+

Body weight

No change

Blood pressure

Visceral adiposity Metabolic syndrome Type 2 diabetes Cardiovascular diseases Stroke

++

Decrease

a

+

Decrease

b

+

Decrease

b

+

Decrease

b

+

Decrease

b

+

, equivocal evidence; +, limited evidence from few studies; ++, evidence from several studies. a Evidence collected from the PREDIMED trial, among others. bEvidence collected only in the PREDIMED trial.

SUMMARY POINTS l

l

l

l l

Nuts, particularly almonds, hazelnuts, pine nuts, pistachios, and walnuts, are integral components of the Mediterranean diet. All nuts are nutrient-dense foods rich in unsaturated fatty acids, protein, fiber, minerals, potent antioxidants, and other beneficial phytochemicals. Prospective studies have associated exposure to nuts with a reduced incidence of CHD in both sexes and of diabetes in women. In RCTs, nut-enriched diets have consistently reduced total and LDL-cholesterol independent of the background diet. The PREDIMED trial has convincingly shown that long-term adherence to a Mediterranean diet supplemented with nuts results in reduced rates of cardiovascular disease, particularly stroke.


l

l

183

A beneficial effect of the nut-enriched Mediterranean diet on metabolic syndrome and diabetes also has been reported by the PREDIMED study. Increasing nut intake does not promote obesity largely because of a pronounced satiating effect.

ACKNOWLEDGMENTS This work was supported in part by grants from ISCIII, Spanish Ministry of Economy and Competitiveness (FIS Thematic Research Networks C03/01 and G03/140), and the California Walnut Commission, Sacramento, CA. CIBERobn is an initiative of ISCIII, Spain.

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