Plant-based diets are growing in popularity globally for an array of reasons which includes concerns for human and planetary health ^[1][2][1,2]. Concepts of what constitutes a ‘plant-based’ diet vary considerably, with present definitions ranging from the elimination of all animal products to diets including dairy, fish and meat in variable amounts [3]. There have been concerns, however, that plant-based diets provide lower levels of the nine essential amino acids (EAA), including specific amino acids, such as leucine, sulphur amino acids and lysine ^[4][5][6][7][4,5,6,7]. Compared with animal-derived proteins it is further alleged that plant-proteins have less of an anabolic effect, due to their lower digestibility and the amino acids being directed towards oxidation rather than muscle protein synthesis (MPS) [7]. It is well appreciated that within the general population misconceptions exist about what constitutes health eating, even more so with goalposts ever shifting in terms of what defines a healthy diet ^[8][9][8,9]. From a consumer behaviour perspective, enjoyment of meat, unwillingness to make dietary changes and health concerns could act as potential obstacles to the shift towards plant-based diets [10]. From a historical standpoint across pre-agricultural hunter-gatherer societies, meat was regarded as a ‘highly prized food’ and today still has strong associations with masculinity [11].

The EAT-Lancet 2019 Food in the Anthropocene report was revolutionary in that it accentuated the need to review food systems and their dual impacts on health and planetary outcomes and included a modelled healthy reference diet that was predominantly plant-based [12]. The EAT-Lancet healthy reference diet advised that this “largely consists of vegetables, fruits, whole grains, legumes, nuts, and unsaturated oils” and as a key message concluded that the transformation to healthy diets by 2050 will require substantial dietary shifts, including a greater than 100% increase in consumption of foods, such as nuts, fruits, vegetables and legumes [12]. Within this guidance, peanuts were listed as a separate protein food source within the legumes category (with a possible daily intake range of 0–75 g) and tree nuts, which would encompass pistachios, were also listed as a separate category (possible intake of 25 g/day) [12]. The EAT Lancet dietary guidance therefore recognises the role of nuts as a key plant protein source.

The Protein Digestibility-Corrected Amino Acid Score (PDCAAS) of only a few nuts has been evaluated. In 2020 a standardised ileal digestibility study measured both the DIAAS and PDCAAS score of raw and roasted pistachio nuts ^[13][56]. Raw and roasted pistachio nuts had a PDCAAS of 73% and 81%, respectively, calculated for children 2–5 years, with the limiting amino acid being threonine in the calculation. The DIAAS was 86 and 83 for raw and roasted pistachio nuts, respectively, calculated for children older than 3 years, adolescents and adults, with the limiting amino acid being lysine ^[13][56]. Taken together, these results demonstrated that both raw and roasted pistachio nuts had a DIAAS greater than 75, thus were recognised as being ‘good quality’ protein sources ^[13][56].

The PDCAAS of other nuts has also been determined. The protein digestibility of cashew nuts, peanuts and Brazil nuts and their PDCAAS have been calculated to be 90.3%, 69.3% and 63.3%, respectively ^[14][57]. For raw almonds, a PDCAAS between 44.3 and 47.8% was equated for children aged 2–5 years ^[15][58]. For walnuts, a PDCAAS of 46% has been calculated for children aged 3–10 years ^[16][38]. In most of these studies the specified limiting EAA was lysine ^[13][14][15][56,57,58]. Researchers have recently compiled a database of amino acids in plant-sourced foods ^[17][59]. The amino acid found to be present in the greatest concentration for both raw and roasted pistachio nuts has been found to be arginine, with leucine being the second most abundant in concentration ^[13][56]. Other research shows that free amino acids represented ≤3.1% of total AAs in pistachio nuts, soybeans, corn grains, white rice and wheat flour and 34.4% and 28.5% in potatoes and sweet potatoes, respectively ^[17][59]. Subsequently, as shown in Table 13, a PDCAAS of 73 and 81%, respectively, for raw and roasted pistachios is higher than scores calculated for almonds, Brazil nuts, peanuts, pecans and walnuts. It is also higher than PDCAAS derived for white rice, chickpeas, red kidney beans and certain lentils (whole green, red and yellow split lentils). The PDCAAS of roasted pistachios was only marginally lower than that of chicken, beef and egg powder. This demonstrates that plant-based pistachios are a balanced and good quality protein source.

There is increased recognition, however, that we should be focusing on the ‘totality of diets’ rather than whether or not individual foods provide all nine EAA ^[27][14]. People ingest mixed diets, thus it is the amino acid composition of the overarching diet that will determine protein adequacy ^[27][14]. Thus, the concept of protein diversification, with protein from a range of food sources beyond those that are animal-derived, is gaining interest ^[28][29][16,17].

As demonstrated in Table 24 different foods provide an assortment of different amino acids. Pistachio nuts are a complete protein providing all nine EAAs along with 4.3 g glutamic acid per 100 g (comparable with beef brisket) and 2.1 g arginine per 100 g (comparable with chicken). After braised beef brisket and cooked chicken, pistachios provide the next highest levels of total EAAs (7.9 g/100 g). Pistachios also provide a higher level of branched chain amino acids compared with other nuts and foods such as brown rice and lentils. Figure 1 further demonstrates that pistachios are an important provider of EAAs.

Mariotti and Gardner (2019) recently explained there have been concerns that amino acid intakes from vegetarian diets are often perceived as being inadequate, but the integration of nuts, seeds, and legumes within diets can be sufficient in terms of achieving full protein adequacy in adults, provided that energy needs are being met and a variety of foods are being consumed ^[30][66]. Pistachios are therefore positioned as a useful protein source, delivering good-quality plant-based protein, fibre, a range of healthy fats, including mono- and polyunsaturated fatty acids whilst being low in saturated fatty acids and providing an array of micronutrients and bioactive compounds ^[31][32][33][25,26,67].

As described, according to European Commission regulations, pistachios are high in’ fibre, monounsaturates, copper, chromium, vitamin B6, thiamine, manganese, phosphorus and potassium and ‘a source’ of protein, vitamin E, K, folic acid, riboflavin, magnesium, iron, zinc and selenium. Pistachios also provide an array of vitamins and minerals alongside anthocyanins, carotenoids, flavonoids and phenolic acids ^[34][35][20,24].

They provide a spectrum of phenolic compounds, with at least 9 lipophilic and 11 hydrophilic bioactive being identified ^[36][80]. Most of the phenolics are present in the skin and the lipophilic constituents tend to be present in the nutmeat ^[36][80]. Research examining the phytochemical profile of American raw and roasted pistachios found that free-form contributions to the total phenolics were 82% and 84% for raw and roasted pistachios, respectively, and free-form contributions to the total flavonoids were 65% and 70% for raw and roasted pistachios, respectively ^[32][26]. For raw and roasted pistachios, gentisic acid and catechin were the predominant phenolics ^[32][26].

Polyphenols in pistachios are known to exert antioxidative and anti-inflammatory effects ^[34][37][20,81] and a range of publications have now documented their wider health effects ^{[31][33][34][37][38]}[20,25,67,81,82].

Several studies have focused on inter-relationships between pistachio ingestion and markers of body weight and composition ^{[39][40][41][42][43][44][45]}[83,84,85,86,87,88,89]. A randomised controlled study found that overweight/obese adults who ingested 42 g/day of pistachios alongside a weight-loss intervention had significantly increased intakes of fibre, ingested fewer sweets, and exhibited similar levels of weight loss to the control ^[39][83].

An extensive 24-week trial recruiting Asian Indians showed that daily consumption of unsalted pistachios (20% energy) significantly improved waist circumference and markers of metabolic syndrome (total-cholesterol, low-density lipoprotein, free fatty acids and adiponectin levels) ^[40][84]. Research with Chinese adults with metabolic syndromes similarly found that ingesting 42 g or 70 g pistachios daily for 12 weeks did not contribute to weight gain nor increased waist-to-hip ratio ^[41][85].

Research focusing on snacking, comparing the ingestion of 53 g of salted pistachios to 56 g of salted pretzels over 12 weeks by obese adults found that BMI declined significantly from 30.1 to 28.8 in the pistachio group compared with a 0.6 decline in the pretzel group ^[42][86]. Other work has shown that amongst healthy-weight women, 44 g (259 kcal) of pistachios daily can improve nutrient intake and induce satiety without impacting on body weight or composition ^[43][45][87,89]. Research by Bellisle et al. ^[45][89] showed that calories provided by pistachio snacks induced satiety and induced energy compensation in healthy women. As an afternoon snack, 56 g of pistachios (versus 56 g energy/protein matched savoury biscuits) did not influence body weight but did improve the micronutrient profile (thiamine, vitamin B6, potassium and copper) of French women, when consumed over four weeks ^[44][88].

Taken together, pistachios may help regulate body weight because of their satiety and satiation effects along with their reduced net metabolizable energy content ^[38][82]. Their fatty acid profile when consumed in moderation does not appear to impact on body weight and should be viewed as a heart-healthy fatty acid profile rather than one posing risk to gains in body weight.

Pistachio constituents possess antioxidant and anti-inflammatory functions which may exert regulatory effects, including glucose- and insulin-lowering effects ^{[34][46][47][48]}[20,21,90,91]. Kendall et al. (2011) ^[49][92] showed that pistachios (28, 56, and 84 g) added to white bread contributed to a dose-dependent reduction in glycaemic responses. The same team later showed that pistachio ingestion (versus white bread) reduced postprandial glycaemia and increased glucagon-like peptide levels ^[50][93]. A publication reanalysing data looking at nuts as a replacement for carbohydrates in diabetes diets further reconfirmed their role in improving glycaemic control in type 2 diabetes ^[51][52][94,95].

The Carlos Gestational Diabetes Mellitus (GDM) prevention study showed that early nutritional intervention with a Mediterranean diet that included pistachios reduced the risk of GDM and improved several maternal and neonatal outcomes, including rates of insulin-treated GDM, prematurity, excess gestational weight gain and rates of small and large-for gestational age infants ^[53][54][55][96,97,98]. Other research ^[56][99] conducted by Feng et al. (2019) investigated the acute effects of two isocaloric test meals—42 g of pistachios and 100 g of whole-wheat bread in Chinese women with GDM or gestational-impaired glucose tolerance. Pistachio intake resulted in significantly lower postprandial glucose, insulin and gastric inhibitory polypeptide and higher glucagon-like peptide-1 levels compared with whole-wheat bread, indicating that these would be a healthy snack choice during pregnancy ^[56][99].

Other factors such as telomere erosion have been linked to type 2 diabetes pathogenesis and severity ^[57][100]. A randomised crossover clinical trial allocated 49 prediabetic adults to consume a diet providing 57 g of pistachios daily or a calorie-matched control diet over four months with a two-week washout period ^[57][100]. The pistachio-supplemented diet significantly reduced DNA oxidative damage and upregulated telomerase reverse transcriptase (TERT) expression, which was inversely correlated to fasting plasma glucose levels ^[57][100]. Other work shows that similar intakes of pistachios (57 g/day) favourably alters microRNA expression linked to insulin sensitivity ^[58][101].

The U.S. FDA authorised the health claims that: “scientific evidence suggests but does not prove that eating 1.5 oz (42.5 g) per day of most nuts, such as pistachios, as part of a diet low in saturated fat and cholesterol may reduce the risk of heart disease” in 2003 ^[59][70].

Nuts are well recognised for their role in reinforcing heart health with a recent meta-analysis showing that nut consumption had a beneficial effect on reducing the incidence of (and mortality from) different cardiovascular disease outcomes ^[60][102]. A meta-analysis of 11 randomised controlled trials demonstrated that pistachio consumption improved cardiometabolic risk factors, including fasting blood sugar, insulin levels, systolic blood pressure and blood lipid profile ^[61][28].

A randomised trial comprised of 30 adults (40 to 74 years) demonstrated that pistachio nut consumption (replacement of low-fat or fat-free carbohydrate snacks with pistachios equivalent to 20% of daily energy (range: 59 to 128 g) depending on calorie assignment) improved certain cardiovascular risk factors, including heart rate variability and systolic blood pressure, with the latter observed most prominently during sleep ^[62][103]. Other early work ^[63][104] showed that diets providing 15% of calories as pistachio nuts (2–3 ounces; 57–85 g per day) improved certain lipid profiles in individuals with moderate hypercholesterolemia.

Ros et al. (2021) concluded that regular nut consumption is an indispensable component of any healthy, plant-based diet and that a daily dose of at least 30 g/d of a mixture of nuts, is ideal for optimising health ^[64][105]. The Global Burden of Disease Study (2017) estimated 21 g per day as the optimal intake of nuts and seeds after evaluating the health ramifications of suboptimal diets ^[65][106].

Subsequently, nuts appear to be an important dietary component for reinforcing heart health. Increasingly, plant-based dietary patterns are being viewed as beneficial for dyslipidaemia management, the prevention of cardiovascular disease risk and being environmentally sustainable ^[66][107].

Tree nut intake has been shown to be associated with a significantly reduced incidence of colon cancer recurrence and mortality ^[67][68][108,109], pancreatic cancer ^[69][70][110,111] and overall cancer mortality ^[71][72][73][112,113,114]. Focusing on pistachios, in vitro and in vivo trials suggest that pistachio consumption could have a beneficial impact on cancer development ^[74][115]. Yuan et al. (2022) extracted free and bound phytochemical compounds in raw and roasted pistachios, finding that these demonstrated potent antioxidant and antiproliferative activities ^[32][26]. The free-form extracts of roasted pistachios exhibited relatively high antiproliferative capacity towards liver HepG2 (a human liver cancer cell line), along with colon Caco-2 and breast cancer MDA-MB-231 cells in a dose-dependent manner ^[32][26]. Of the extracts tested, roasted free extracts exhibited higher anticancer activities although free extracts of roasted pistachios had exceptionally high activity against human breast cancer MDA-MB-231 cells ^[32][26]. Other research by Glei et al. (2017) demonstrated chemopreventive potential of pistachio nuts using in vitro colon adenoma cells ^[74][115]. This effect was mediated by growth inhibition, the induction of apoptosis and anti-genotoxic effects, along with the induction of detoxifying enzymes ^[74][115]. Work has further shown that fermented pistachio milk possesses anti-colon cancer properties, which could be attributed to its acetate content ^[75][116].

Pistachios and pistachio extracts appear to play further roles in cognitive function, inducing neurobehavioral and neurochemical modifications ^[76][77][117,118] and exerting anxiolytic (anti-anxiety) effects ^[78][79][119,120]. Pistachio consumption also been linked to restoration of gut microbiota composition, with improved Bifidobacterium, Lactobacillus, Turicibacter and Romboutsia (beneficial bacteria) profiles ^[80][81][121,122]. Interestingly, after four weeks of prediabetic adults ingesting 57 g/day of pistachios, the urine profile of gut-microbiota metabolites altered significantly ^[82][123]. Further research has found that the ingestion of mixed tree nuts (1.5 oz over 12 weeks) affects tryptophan and microbial metabolism in overweight and obese subjects ^[83][124]. Changes in gut microbiota is an emerging area of research needing more attention.