Nutrition attributes and health effects of pistachio nuts

The present review examines the potential health effects of compounds in pistachios as well as epidemiological and clinical evidence supporting the health benefits of pistachio consumption.

Protein

Pistachios are a good source of vegetable protein, which comprises about 20 % of total weight, with approximately 2 % l-arginine⁽²¹⁾. This amino acid, also present in other nuts, is a precursor to the endogenous vasodilator NO, an important molecule involved in the cardiovascular system as a key regulator of vascular tone and in numerous pathological conditions such as hypertension, CVD and neurodegenerative disorders due to its pro-oxidant capacity^{(22, 23)}. NO synthase inhibitors based on arginine have been of special interest for experimental as well as clinical applications⁽²⁴⁾. Therefore, pistachios could play an important protective role in NO synthase-related diseases. On a per serving basis (28·35 g), pistachios provide 10·6 % US RDA of adult men and 12·9 % of adult women⁽²⁵⁾. Compared with the FAO- and WHO-recommended essential amino acid pattern for an adult, pistachios contain adequate amounts of all of the essential amino acids⁽²⁶⁾. Pistachios have an essential amino acid ratio (essential amino acid:total amino acid) of 39·1, higher than most of all the commonly consumed nuts (almonds, walnuts, pecans and hazelnuts). Pistachios also provide a high percentage of branched-chain amino acids (1·599 g leucine, 0·932 g isoleucine and 1·262 g valine per 100 g), higher than other tree nuts.

Carbohydrates and fibre

The amount of carbohydrate in pistachios, as in other nuts, is low to moderate (about 27·5 % by weight), but pistachios are rich in fibre, containing 10 % by weight of insoluble forms and 0·3 % of soluble forms. Pistachios provide 3 g or 12 % of RDA per serving basis (Table 1)⁽¹⁰⁾. According to the US Department of Agriculture food composition tables, of all nuts, only almonds have similar amounts of fibre, with 13 % of weight. Fibre content is important because epidemiological and clinical studies have consistently demonstrated that fibre intake is inversely associated with weight gain⁽²⁷⁾, diabetes⁽²⁸⁾, CVD⁽²⁹⁾ and some types of cancer⁽²⁸⁾. Moreover, pistachios have a low glycaemic index, which contributes to maintaining satiety longer and lowering postprandial blood glucose concentrations^{(30, 31)}.

Vitamins and minerals

Pistachios are rich in Cu, Mg, Mn, vitamin A, vitamin C and B vitamins, with the exception of vitamin B₁₂ (cyanocobalamin)⁽³²⁾, compared with other nuts (Table 3). In particular, pistachios contain relatively high amounts of thiamin (vitamin B₁), which is involved in intermediary carbohydrate metabolism, with 0·87 mg/100 g of pistachios (providing up to 50 % of the RDA). The amount of pyridoxine (vitamin B₆) that is involved in the metabolism of amino acids and in the production of niacin is about 1·7 mg/100 g of pistachios, exceeding the RDA. Finally, the amount of folic acid in pistachios provides approximately 25 % of the RDA. Folic acid is necessary for the formation of structural proteins and Hb, and deficiency leads to an increase in the risk of CVD⁽³³⁾. Among nuts, pistachios also stand out for high vitamin K content, with approximately 13·2 μg/100 g (16 % of the RDA; Table 3). Beyond its role in bone metabolism^(34-36), a higher dietary intake of vitamin K has been associated with a lower risk of several chronic diseases such as type 2 diabetes (T2DM)⁽³⁴⁾, cancer^{(37, 38)} and CVD⁽³⁸⁾, thus expanding the potential health benefits of pistachio consumption. The beneficial role of pistachios in inflammatory-related diseases may also be explained by the relatively high amount of γ-tocopherol they contain⁽³⁹⁾.

Pistachios are rich in several minerals such as K, Mg, Ca, Cu and Mn. Because of their mineral profile, pistachios could play a beneficial role in blood pressure (BP) regulation or in bone-related diseases. Pistachios also contain significant amounts of Zn and Se, both minerals with recognised antioxidant effects that are involved in the prevention of CVD and some types of cancer^{(40, 41)}.

Phenol content

Pistachios, pecans and walnuts are rich sources of phenolic compounds, including anthocyanins, flavonoids, proanthocyanidins, flavonols, isoflavones, flavanones, stilbenes, phenolic acids and hydrolysable tannins, which are important as antioxidants and also for their chemopreventive, cardioprotective and vasoprotective properties^{(42, 43)}. Phenolic compounds may have protective effects against diseases related to free radical overproduction, such as CVD and cancer. A randomised, double-blinded, cross-over study with placebo v. a supplement of 640 mg anthocyanins daily during 4 weeks in pre-hypertensive men showed a significant increase in HDL-cholesterol (HDL-C) levels and also blood glucose levels after anthocyanin v. placebo treatment⁽⁴⁴⁾. Furthermore, the hydrophilic extract from pistachios, which has high antioxidant activity, increases the resistance of human LDL-cholesterol (LDL-C) from healthy subjects to Cu-induced oxidation after 2 h of incubation⁽⁴⁵⁾.

According to Tomaino et al. ⁽⁴⁶⁾, all phenolic groups found in pistachios, and in other nuts, are present in higher amounts in the skins than in the seeds. Pistacia vera L. (variety Bronte) skins contain cyanidin-3-O-galactoside (5865 mg/g), gallic acid (1453 mg/g), catechin (377 mg/g) and eriodictyol-7-O-rutinoside (366 mg/g). Pistachio kernels contain quercetin-3-O-rutinoside (98·1 mg/g), genistein (69·1 mg/g), genistein-7-O-glucoside (47·0 mg/g) and daidzein (42·4 mg/g). Therefore, the final content of total flavonoids in the skins is 70·27 (sd 5·42) mg of catechin equivalents/g of fresh weight, whereas in the seeds, it is only 0·46 (sd 0·03) mg of catechin equivalents/g of fresh weight⁽⁴⁶⁾. Pistachios are the only nut containing anthocyanins, phenolic compounds, in the skin. These phenolic compounds are known to bind metals through binding with o-diphenol groups, which is important in the inhibition of metal-induced lipid oxidation⁽⁴⁷⁾. Nonetheless, in a simulated human digestion model, more than 90 % of the pistachio polyphenols were released to the gastric compartment without differences between raw or roasted pistachios^{(12, 48)}.

Carotenoids

Lutein and zeaxanthin are two xanthophyll carotenoids responsible for giving colour to pistachio nuts. Raw pistachios contain 1405 μg lutein+zeaxanthin/100 g, about thirteen times more than the next highest nut type, hazelnuts, which contain only 92 μg (Table 3). The bioavailability of carotenoids depends on the source and interaction with other dietary components. Van Het Hof et al. ⁽⁴⁹⁾ demonstrated that the interaction of β-carotene and lycopene with the lipid matrix increases the bioavailability of carotenoids. Notably, almost 100 % of the bioaccessibility of lutein was found after in vitro duodenal digestion⁽¹²⁾. Carotenoids have antioxidant properties and have been associated with a reduced risk of CVD and some types of cancer⁽⁴⁹⁾. Moreover, lutein and zeaxanthin are concentrated in the retina where they thought to function as antioxidants and/or as a blue light filter, to protect the underlying tissues from phototoxic damage⁽⁵⁰⁾. This has been proposed as an important factor in the pathophysiology of age-related macular degeneration⁽⁵¹⁾.

Total phytosterols

Among nuts, pistachios have the highest phytosterol content, with 214 mg/100 g, including stigmasterol, campesterol and β-sitosterol. Phytosterols, structurally similar to cholesterol, have the same basic cyclopentanoperhydrophenanthrene ring structure but differ in the side chain at C24 and/or the position and configuration of unsaturated double bonds and the optical rotation at chiral carbons. Several studies have demonstrated a dose–response reduction of cholesterol mediated by phytosterols, even at lower levels similar to those found in plant-based diets with pistachios⁽⁵²⁾. Although 500 mg of phytosterols per serving are needed to support the Food and Drug Administration (FDA) health claim, the levels of phytosterols in pistachio nuts may be sufficient to play a synergistic role with unsaturated fatty acids and the low SFA levels in helping to maintain normal cholesterol levels.

Several biological mechanisms may explain the unexpected null effect of nut consumption on adiposity. Nuts are rich in unsaturated fatty acids, and evidence suggests that MUFA and PUFA are more readily oxidised⁽⁸⁴⁾ and have a greater thermogenic effect⁽⁸⁵⁾ than SFA, which can lead to less fat accumulation. Several lines of evidence also demonstrate that nuts have high satiety properties. Nuts are energy dense and a good source of fibre, protein and unsaturated fats, dietary factors that increase satiety ratings. Nuts exert a strong suppression of hunger and therefore subsequent food intake is curtailed^(86-88). In fact, two recent published studies have evaluated the satiating properties of pistachio nuts. The impact of consuming in-shell pistachios or pistachio kernels on fullness and energy intake was evaluated in a randomised, cross-over, controlled feeding trial including 140 university students aged 18–24 years. Consumption of in-shell pistachios resulted in a lower energy intake than consumption of kernels⁽⁸⁹⁾. The same authors, in a second cross-over feeding trial with 118 healthy individuals (mean age 47 (sd 10) years), demonstrated that the visual cue of the empty pistachio shells may have helped the participants to consume fewer pistachios and about 18 % less energy⁽⁹⁰⁾ (Table 5).

The physical structure of nuts may also contribute to their satiety effect; they are crunchy and must be mechanically reduced to particles small enough for swallowing. Mastication activates mechanical, nutrient and sensory signalling systems that may modify appetitive sensations⁽⁹¹⁾.

Furthermore, a small degree of fat malabsorption has been reported after nut intake, which is attributed to the fat being contained within walled cellular structures that are incompletely digested in the gut, an effect that can be compounded by incomplete mastication⁽⁹²⁾. In fact, a cross-over trial conducted on sixteen healthy volunteers consuming pistachios (42 and 84 g/d) or a free-nut diet for 3 weeks, as part of a controlled diet, demonstrated that the metabolisable energy of pistachios, calculated from differences in faecal energy excretion during the different dietary treatments, is 5 % less than the energy calculated by the Atwater general factors, suggesting that the energy from pistachios is not totally utilisable⁽⁹³⁾.

Classical markers of CVD

In a pooled analysis of twenty-five intervention trials, participants who consumed an average of 67 g/d of nuts saw a 5 % decrease in total cholesterol, a nearly 7·5 % decrease in LDL-C levels and an 8 % decrease in the LDL-C:HDL-C ratio. The effects of nut consumption were dose-related, and different types of nuts had similar effects on blood lipid levels⁽⁹⁴⁾. The effect of pistachio consumption on cardiovascular risk markers has been evaluated in five randomised clinical trials as a primary outcome^(79-83) and in other studies as a secondary outcome^{(73, 76, 95)}, giving from 10 to 20 % of energy or from 42 to 100 g/d as pistachios v. diets avoiding the consumption of nuts (Table 4). From them, in a total of five studies, the authors found significant reductions in plasma total cholesterol concentrations in the pistachio-supplemented group^{(79, 80, 82, 83, 95)}, and in six of them, they found a significant reduction in the total cholesterol:HDL-C ratio and LDL-C:HDL-C ratio^{(79-83, 95)}. Moreover, LDL-C concentrations were decreased in the pistachio-supplemented group in three studies^{(82, 83, 95)}, whereas two studies reported no significant reductions in this recognised major cardiovascular risk factor^{(79, 80)}, although the levels decreased but not significantly in Kocyigit et al. ⁽⁸⁰⁾. Only Wang et al. ⁽⁷⁶⁾, in a study of Chinese subjects with the metabolic syndrome, found an increase in plasma LDL-C levels after a 12-week period of dietary intervention with a normoenergetic diet including different amounts of pistachios compared with the normoenergetic diet alone. According to Wang et al. ⁽⁷⁶⁾, the nutrient content of the diet was underpowered to show changes in the secondary analyses of risk factors such as blood lipids. Notably, dietary intake was not controlled or reported, so it is difficult to ascertain the reason why LDL-C levels increased in the high-pistachio group. With respect to plasma HDL-C, only Sheridan et al. ⁽⁸¹⁾ found a significant increase in this parameter in those subjects supplemented with pistachios.

A beneficial effect of pistachios on BP has also been demonstrated recently in a randomised, cross-over, clinical trial conducted on twenty-eight dyslipidaemic individuals. Participants were randomised to three 4-week interventions: a low-fat control diet; a diet containing 10 % of the total energy content in the form of pistachios; a diet containing 20 % of the total energy as pistachios. A dose-dependent reduction in systolic BP was observed in those subjects supplemented with pistachios, and a decrease in peripheral vascular dilation was observed in those supplemented with higher doses of pistachios⁽⁹⁶⁾. The BP-lowering effects of pistachios have also been evaluated in three additional controlled feeding trials as a secondary outcome showing non-significant differences in the changes in systolic or diastolic BP between those subjects supplemented with pistachios and those who did not receive supplementation^{(76, 81, 83)}.

In conclusion, some evidence suggests that pistachios may improve the blood lipid profile and reduce BP, which could contribute to decreased cardiovascular risk.

Emerging risk factors of CVD

Pistachios are a rich matrix of fat-soluble antioxidants that could have important effects on the control of oxidative stress and a reduced risk of chronic diseases. In a study conducted on forty-four healthy men and women, half of the subjects were randomised to a regular diet group and the other half to a pistachio group (accounting for 20 % of their daily energy intake in the form of pistachios) for 3 weeks. The study showed an increased blood antioxidant potential determined by the production of thiobarbituric acid-reactive substances and decreased malondialdehyde levels, which is an important indicator of lipid peroxidation, in those volunteers consuming pistachios compared with those following a free-nut diet⁽⁸⁰⁾. A cross-over, randomised, controlled feeding trial conducted by Kay et al. ⁽⁹⁷⁾ on twenty-eight hypercholesterolaemic adults showed that the consumption of diets containing 10 and 20 % of energy from pistachios (32–63 and 63–126 g/d, respectively) increased antioxidant concentrations in serum, such as γ-tocopherol, lutein and β-carotene, whereas it decreased oxidised LDL concentrations relative to the consumption of a control diet without pistachios. Finally, in a prospective study, Sari et al. ⁽⁸³⁾ assessed the effect of a traditional Mediterranean diet supplemented with pistachios by replacing the monounsaturated fat content constituting approximately 20 % of daily energy intake on thirty-two healthy young men for 4 weeks. They found a significant improvement in endothelium-dependent vasodilation, whereas endothelium-independent vasodilation remained unchanged compared with the Mediterranean diet. An increase in total antioxidant status and superoxide dismutase and a decrease in inflammation and other oxidative markers were also observed. Taken together, these results provide evidence of the beneficial effects of pistachios on the risk of CVD beyond the lipid-lowering effect.

Insulin resistance and type 2 diabetes

Diabetes mellitus is one of the most common diseases worldwide, largely the result of an increase in the prevalence of obesity and physical inactivity. Moreover, T2DM is a recognised risk factor for CVD and other chronic conditions and diseases, and is thus becoming a serious public health burden^{(98, 99)}. Data from epidemiological and interventional studies suggest that the frequency of nut consumption is inversely related to an increased risk of T2DM, mainly attributed to the fibre, healthy fats, antioxidants and anti-inflammatory compounds^{(72, 100-104)} in nuts. In addition, among all nuts, pistachios have a low glycaemic index, suggesting a possible effect on reducing postprandial glycaemia and insulinaemia, thereby potentially decreasing the risk of diabetes. The effect of pistachios, consumed alone or combined with meals, on postprandial glycaemia has been evaluated^{(30, 105)} (Table 5). Thus, whereas pistachios consumed alone had a minimal effect on postprandial glycaemia, the addition of pistachios (56 g) to foods with a high glycaemic index (pasta, parboiled rice and instant mashed potatoes) reduced, in a dose-dependent manner, the total postprandial glycaemic response by 20–30 %⁽¹⁰⁵⁾. In a recent randomised, cross-over study conducted on twenty subjects with the metabolic syndrome, 85·04 g of pistachios consumed with bread reduced postprandial glycaemia levels and increased glucagon-like peptide levels compared with bread alone⁽³⁰⁾.

In three clinical studies, the effect of pistachio supplementation on glucose concentrations as a secondary outcome was evaluated, with contradictory results. In a controlled, cross-over, clinical trial, participants were randomised to a Mediterranean diet or a Mediterranean diet supplemented with 20 % of energy intake as pistachios for 4 weeks in each arm. Subjects in the intervention period showed a significant decrease in fasting plasma glucose concentrations in comparison to the control period⁽⁸³⁾. The second study evaluated the effect of the American Heart Association Step I diet supplemented with 42 or 70 g/d of pistachios compared with the effect of a control diet (American Heart Association Step I), in Chinese subjects with the metabolic syndrome using a randomised, parallel-group, controlled study design. After 12 weeks of intervention, no differences in fasting plasma glucose or insulin levels were observed between the groups, although compared with baseline values, blood glucose levels increased significantly in the control group at week 12 but not in the two pistachio groups⁽⁷⁶⁾. Finally, in a third parallel study conducted on sixty subjects with the metabolic syndrome randomised to either an unsalted pistachios diet (20 % energy) or a control diet for 24 weeks, a significant decrease in glucose levels but not in blood insulin levels was observed⁽³¹⁾.

In addition to the fibre, healthy fats and low available carbohydrate content, the effect of pistachios on glucose metabolism may be a result of the rich content of carotenoids. A 9-year longitudinal study conducted on 1389 healthy elderly volunteers demonstrated a 58 % lower risk for the development of impaired fasting glucose levels or T2DM mellitus in subjects in the highest quartile of total plasma carotenoids than in those in the lowest quartile, even after adjusting for possible confounding variables⁽¹⁰⁶⁾. In a randomised controlled study, the intake of 75 g/d of mixed nuts (including pistachios) in 117 T2DM subjects during 3 months as a replacement for carbohydrate-containing foods in comparison to the intake of healthy whole-wheat muffins, or half portions of both, demonstrated for the first time a significant decrease in HbA_1c levels, even though the subjects were on oral antidiabetic medication. Additionally, and despite the subjects consuming statins, an improvement in total cholesterol was observed⁽³⁾.

Despite the positive results observed for glucose metabolism in fasting conditions or postprandial status, more studies are necessary to evaluate the long-term effects of pistachio consumption on insulin resistance, secretion or diabetes control.

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