Health Benefits Related To Tree Nut Consumption And Their Bioactive Compounds

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2.5.Functional Food Properties

Tree nuts, mainly almonds and pistachios, have a positive effect on the composition of the bacterial and fungal fecal microbiota(Table 5). Several studies pointed out the potential of nut or/and the nuts skin, especially almond skin, to be used as source of prebiotics [24,25,27], due to non-bioaccessible nu-trients and phytochemicals in nuts such as polymerized polyphenols, ellagitannins, and proanthocyanidins, which are the fiber that enter the colon intact [61].

Mandalay et al. showed that finely ground almonds (FG) subjected to a combined model of the gastrointestinal tract that included in vitro gastric and duodenal digestion, when used as substrates for the colonic model to assess their influence on the composition and metabolic activity of gut bacteria populations, increased the populations of bifidobacteria and Eubacterium rectale, resulting in a high prebiotic index. No effect was observed when using defatted finely ground almonds (DG) [25]. The authors highlighted the lipid component of almond seeds as a relevant element in the alteration of bacterial growth and metabolism, given that only a small amount of almond lipids and proteins are bioavailable during gastric and small intestinal digestion due to nutrient encapsulation by cell walls likely to prevent digestion in the upper GIT [26]. In another study using an in vitro gastric and duodenal digestion model, followed by colonic fermentation, the potential prebiotic effect of almond skins, by-products of industrial blanching, was also proven. cistanche life extension The study showed the ability of natural (NS) and blanched (BS) almond skins to significantly increase in vitro the bifidobacteria and Clostridium coccoides/Eubacterium rectale numbers. This highlighted the beneficial effects of the nonglycemic carbohydrates, mainly pectin, present in almond skins and showed that polyphenols, present in almond skins, did not affect bacterial fermentation [27]. Furthermore, almond skins have been shown to have high fiber content as well as significant amounts of lipids; both of these components may be relevant to fermentation in the large intestine [28].

A very recent randomized study enrolling 102 participants with HIV demonstrated that a Mediterranean diet, supplemented with extra virgin olive oil and walnuts, may improve metabolic indicators, immune activation, and gut microbiota diversity for people affected with HIV-1 [62]. The authors showed an improved lipid profile, whereas the immune activation and IFN-y-producing T-cells were reduced in the group supplemented with olive oil and walnuts.

Recently, the effect of pistachio consumption on gut microbiota composition has been reported. The characterization of microbiota in fecal samples collected from volunteers who were recruited to participate in two separate randomized, controlled, crossover studies was carried out. The subjects were assigned to three treatment groups:no nuts;15 servings/d either almonds or pistachios and 3 servings/d of either almonds or pistachios; the feeding periods were separated by a washout period of at least 2 weeks It has been shown that the effect of pistachio consumption on gut microbiota composition was stronger than almond and included an increase in the number of potentially beneficiall butyrate-producing bacteria [24].

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Other studies are consistent with these findings, showing how the abundance of dietary fiber and polyphenols may be correlated to the prebiotic effects of almond skins and almonds [23].

Liu et al. compared the daily supplementation of roasted almonds (56 g), and almond skins (10 g) in the diet of 48 healthy adult volunteers, for 6 weeks, to a commercial fructooligosaccharides (8 g) supplementation. The almond and skin intake promoted significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. cistanche nz in fecal samples, while the growth of the pathogen Clostridum perfringens was significantly repressed and Escherichia coli numbers did not change significantly, compared to the control [23]. Dhillon et al. (2019) also demonstrated that almond snacking in 73 college freshmen for 8 weeks increased the alpha-diversity of the GI microbiome and significantly decreased Bacteroides fragilis abundance compared [63].

2.6.Cognitive Performance of Nuts

Almonds are rich in nutrients that benefit cognitive function. A number of studies have identified an effect of almond consumption on cognitive performance (Table 6). A recent study [64] reported on the effects of daily almond consumption for six months on cognitive measures in healthy middle-aged to older adults through a random-ized control trial: results confirmed that although serum markers of inflammation and oxidative stress were not significantly affected across the groups, there was a significant improvement in visuospatial working memory, visual memory and learning, and spatial planning and working memory in subjects receiving almonds. Furthermore, the serum alpha-tocopherol concentrations increased by 8 percent in the almond group only. Coates et al. examined supplementing habitual diets with either almonds or carbohydrate-rich snack foods on biomarkers of cardiovascular and metabolic health, mood, and cognitive per-formance in overweight/obese people,50-80 years old [65]. While the almond-rich diet significantly reduced triglycerides, no other changes in cardiometabolic biomarkers, mood, or cognitive performance were detected. In a randomized trial with overweight and obese adults, Dhillon et al. observed that the consumption of an almond-enriched high-fat lunch ameliorated the post-lunch dip in memory, although it did not further enhance the cognitive function outcomes with weight loss over 12 weeks [66].

When 522 participants at high vascular risk from a primary prevention trial (PRED-IMED) followed a nutritional intervention comparing two MedDiets(supplemented with either extra-virgin olive oil (EVOO) or mixed nuts) versus a low-fat control diet, higher mean Mini-Mental State Examination (MSE) and Clock Drawing Test (CDT) scores were recorded with either EVOO or nuts. Therefore, nuts appeared to improve cognition com-pared with a low-fat diet [67]. In another study, the same authors reported no significant differences in cognitive performance and cognitive status (normal, mild cognitive impair ment, or dementia) in participants assigned to the MedDiet plus Nuts group [68]. Another randomized controlled trial to define the effect of the Mediterranean diet on cognitive func-tion enrolling older women identified no association between total nut intake and global cognitive function [69].

A cross-sectional study performed in Northern Italy involving 279 participants aged >65 years (80 men,199 women) was carried out to determine adherence to the Mediterranean diet and its association with cognitive function [70]. Results showed that nut consumption was associated with a lower risk of cognitive impairment (OR=0.30;95% CI,0.13-0.69, p =0.005). Another Italian-based study enrolling 119 older participants concluded that nut consumption estimated either by the dietary marker or by the urinary marker model was associated with less cognitive decline (OR:0.78,95% CI:0.61,0.99;p=0.043 and OR:0.995 95%CI:0.991,0.999;p=0.016,respectively) with AUCs73.2(95% CI:62.9,83.6) and 73.1 (62.5,83.7),respectively[71]. The Hordaland Health Study assessed cognitive performance among the elderly in relation to the intake of plant foods, including fruits, vegetables, potatoes, grain products, mushrooms, and nuts[72]. No significant differences were observed between groups af consumption of nuts, whereas subjects with intakes of >10th percentile of fruits, vegetables, grain products, and mushrooms performed significantly better in cognitive tests.

In an animal study employing healthy rats,repeated administration of almonds was shown to increase brain acetylcholine levels and enhance memory function. The memory deficits were also attenuated [73]. Another animal study evaluated the almond consumption in scopolamine-induced amnesia in rats [74]. The authors detected a significantly reversed scopolamine (1 mg/kgip.)-induced amnesia after 7 and 14 days of almond ad-ministration. The brain cholinesterase activity was also reduced after almond consumption, together with a cholesterol and triglyceride lowering property and a slight increase in glucose levels.

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Taken together, these reports show a positive effect of almond consumption in animal studies and in certain clinical trials, indicating the need to define the impact of the study time frame, age of participants, and any pre-existing metabolic disorder. These factors, together with changes through dietary manipulation, may affect cognition measures. A cross-sectional study on the relationship between walnut consumption and cognitive function indicated positive associations among all adults, regardless of age, gender, or ethnicity, suggesting that daily walnut intakecould be a beneficial dietary behavior [75]. In particular, adults aged 20-59 years old required 16.4 ms less time to respond on the simple reaction time and 0.39 s less for the symbol digit substitution after consuming an average of 13.1 g walnuts per day. The effects of walnut consumption on cognitive performance in young adults has also been established by Pribis et al. through a randomized controlled trial: although no significant increases were detected for mood, non-verbal reasoning or memory as a result of the walnut-supplemented diet, inferential verbal reasoning increased significantly by 11.2 percent [76]. A recent study with a representative sample of 3632 US adults aged 65 years and older established an association between walnut consumption and cognitive function, with greater cognitive scores in volunteers consuming walnuts [7]However, walnut consumption was not protective against age-related cognitive decline. Chauhan and Chauhan [78] have also recently reported on the beneficial effects of walnuts on cognition and brain health, highlighting the benefits of a walnut-enriched diet in brain disorders and in other chronic diseases. An animal study suggested that dietary supplementation with walnuts may have a beneficial effect in reducing the risk, delaying the onset, slowing the progression of, or preventing Alzheimer's disease [79]. In another study with aged rats (19 months old), a diet supplemented with 6 percent walnuts was reported to improve cognitive and motor performance [80].

Fewer studies are available in the literature on cognitive performance related to pistachio consumption. cistanche penis size However, significantly positive outcomes were detected in a number of animal studies [81,82]. In a recent study, Nuzzo et al. demonstrated that a regular intake of pistachios mitigated the effects of a high-fat diet (HFD)in the brain of obese mice: the pistachio diet significantly reduced the serum levels of triglycerides and cholesterol in the HFD model, whereas no significant differences were observed in insulin resistance between the two diets. cistanche powder Furthermore, the impaired mitochondrial function found in HFD brain was partially recovered after the pistachio diet, together with a decrease in reactive oxygen species, singlet oxygen, and phosphorylated extracellular signal-regulated kinase. A positive outcome was also revealed in male rats subjected to treatment with cisplatin or vincristine whose diet was supplemented with pistachio (10 percent ) to attenuate motor and cognition impairments[82].

The potential of Pistacia vera fruits in experimental memory impairments was assessed in Swiss Albino mice whose memory impairment was induced by scopolamine [83]. Pre-treatment of mice with an ethanolic fraction of Pistacia vera fruit significantly reduced scopolamine-induced amnesia, with an increase in escape latency and in step-down latency. The demonstrated cognitive improvement was related to treatment with Pistacia vera fruits. In a randomized controlled trial, the consumption of brazil nuts provided some evidence of positive cognitive effects on verbaal fluency and constructional praxis compared with the control groups[84].

Given the limited literature data on the cognitive performance of certain tree nuts, we believe it would be worthwhile to explore their potential in the management of memory disorders in humans.

Bioactives Related to Cognitive Function

The perfect functionality of our brain is perhaps one of the most important elements for the regulation of our body and its performance. The brain requires a high amount of energy, which is mainly supplied by glucose. Since neurons are particularly susceptible to oxidative stress, foods rich in omega-3 fatty acids, such as nuts, may help build and repair the brain damaged cells. Phenols, polyphenols,and vitamins also reduce cellular oxidative stress onset, inflammation, and activation of the apoptotic pathway, which could be directly linked to brain aging and neurodegeneration [85-90]. In general, seeds are a rich source of several "brain-friendly" compounds, including natural oils [86,91]. However, what are these active compounds, and how do they act to keep our brain sharp and in good health?Nuts are particularly rich in both MUFA and PUFA, phenols and polyphenols compounds, minerals and vitamins, such as vitamin E [92-94]. The junction between a balanced diet,an active life style, and the assumption of these compounds will have a role in boosting the brain performance and memory [69,95]. Although so far, literature studies are very limited, some interesting results can be found in epidemiological and experimental works (with both in vitro and in vivo data). Given the high amount of omega-3 fatty acids, vitamin E and antioxidants, nuts can protect neurons from free radicals and other reactive oxygen and nitrogen species (ROS and RNS) and slow down cognitive decline. Moreover, other compounds, such as riboflavin and L-carnitine, may have an effect on brain function, since they are involved in the development of neural pathways [86,96]. The antioxidant and anti-inflammatory components in walnuts, which include flavonoids, phenolic acid (ellagic acid),melatonin, folate, vitamin E, selenium, proanthocyanidins, and w-3 -linolenic acid have also been reported to act additively or synergistically to reduce the risk of age-related diseases[78].

Another class of compounds with a potential effect on cognitive function is carotenoids such as lutein and zeaxanthin, whose chemical structure allows it to act as efficient singlet oxygen and peroxyl radical scavengers. Amongst tree nuts, lutein and zeaxanthin are found in pistachios. A randomized, double-masked, placebo-controlled trial involving supple-mentation with lutein/zeaxathin to evaluate the cognitive function of community dwelling older adults showed that participants receiving the supplementation had statistically sig-nificant increases in macular pigment optical density, improvements in complex attention and cognitive flexibility domains, as well as executive function domain [97]. Moreover, the supplementation improved composite memory in male participants. Lutein is a natural dietary antioxidant that could help maintain the brain structure by lowering the level of oxidative stress and related damages [98] as well as chronic inflammation. Indeed, it has been demonstrated that lutein and zeaxanthin are well-known strong anti-inflammatory molecules [99]. Moreover, Johnson and colleagues showed that lutein can be identified in higher concentration in the brain compared with peripheral blood circulation, as assed using matched brain tissue and serum samples in a group of centenarians [100]. The effects of these compounds have also been analyzed in several studies on young people. For instance, preliminary data showed that supplementation with lutein and zeaxathin in-creased systemic levels of brain-derived neural growth factor in younger individuals [101]with increased visual processing speed and reaction times [102,103]. The mechanisms underlining these effects are not yet clear; it has been only speculated that the effect can be due to an influence on processing speed and brain connectivity [104], perhaps by enhancing gap junctions between neurons. Almond consumption may have an indirect effect on brain cognitive functions based on its effectiveness in weight loss [105,106]. Studies based on weight loss intervention including almonds also reported an improvement in memory and attention, due to weight loss, and a reduction of the post-lunch dip in memory [65,66,107]. cistanche salsa extract Kulkarni et al. found a direct effect of almond intake and scopolamine-induced amnesia in rats [74]. The oral administration of three doses (150,300,and 600mg/kg) for7 and 14 consecutive days to the respective groups of rats resulted in the reversion of scopolamine(1 mg/kg i.p.)-induced amnesia, as evidenced by a decrease in the transfer latency in the EPM task and step-down latency in the passive avoidance task. Moreover, oral administration of almonds resulted in a reduction of brain cholinesterase activity ir rats, together with a remarkable decrease of blood biochemical parameters, such as cholesterol and triglyceride lowering, and a slight increase in glucose levels.

2.7.Miscellaneous

The effects of almond consumption on skin lipids and wrinkles have been investigated in a randomized controlled pilot study enrolling 50 healthy postmenopausal females:the natural antiaging benefits of almonds were reflected on the significant reduction of wrinkles severity [108]. Another recent randomized controlled trial concluded that the daily consumption of almonds could contribute to the improvement of facial wrinkles and reduction of skin pigmentation in postmenopausal women with Fitzpatrick skin types I and Ⅱ[109]. Furthermore, recent findings suggested that daily oral almond consumption was related to enhanced protection from UV photodamage in healthy Asian women [110]These data support our previous investigation on the photoprotective effect of blanch water, which is a by-product of the almond processing industry [1]

Almonds are a rich source of magnesium, whose consumption from dietary sources has been shown to be beneficial in reducing cancer mortality [112]. Furthermore, a recent systematic review comprehensive of 49 clinical trials reported a beneficial effect of oral prescribed magnesium therapy against hypertension [113].

A number of studies have indicated that walnuts provide key nutrients, such as alpha-linolenic acid, which can help with the male reproductive system. A randomized controlled trial demonstrated that walnuts added to a Western-style diet improved sperm vitality, motility, and morphology [114]. These findings have been corroborated by some animal studies, supporting the evidence of the effectiveness of walnuts on sperm quality [115,16].

A randomized controlled study has reported the beneficial effects of a Mediterranean diet with additional extra virgin olive oil and pistachios on gestational diabetes mellitus, whose prevalence is increasing and becoming a major public health concern [117]. These data are supported by a later study showing that pistachios are an effective alternative to a low-fat, high-carbohydrate food in order to improve postprandial glucose, insulin, and GLP-1 response in women with gestational diabetes mellitus and with gestational impaired glucose tolerance [118].

3. Conclusions

The available scientific evidence on the health benefits related to nut consumption has indicated an effect on cardiovascular and chronic disease prevention, anti-inflammatory and oxidative stress reduction, as well as functional food properties. Although studies investigating the effect of nuts in counteracting the impact of brain aging are more limited and often controversial, the presence of mono- and poly-unsaturated fatty acids, together with minerals, vitamins, and polyphenols could play an important role in cognitive performance, with an impact on aging and neurodegeneration. Lutein in pistachios is also a novel phytochemical affecting cognitive function.

This article is extracted from Int. J. Mol. Sci. 2021, 22, 5960. https://doi.org/10.3390/ijms22115960 https://www.mdpi.com/journal/ijms