The ND is rich in vegetables and fruits which are the main sources of nutritious components such as minerals, natural antioxidants, vitamins, and dietary fibers (58, 59). These components have multiple beneficial effects in preventing and improving several chronic disorders. Their benefits for health are mediated by polyphenolic compounds to provide antioxidant, anticarcinogenic, antimicrobial, antiviral, and anti-inflammatory effects (58, 60–62). Thus, daily consumption of foods rich in plant-derived polyphenols has been encouraged, especially in the Western world (61, 63).

Berries are important and abundant wild fruits in the Nordic countries with significant health-promoting outcomes, attributed mainly to a special class of polyphenols known as anthocyanins (64). Anthocyanins are organic water-soluble glycosidic pigments widely found in dark-colored vegetables, fruits, and grains with considerable inherent antioxidant properties (65). It has been reported that anthocyanins have a wide and various range of beneficial impacts such as anti-inflammatory, immunomodulatory, cardioprotective, hepatoprotective, neuroprotective, anticancer, antidiabetic, anti-obesity, and antioxidant effects, which make them promising factors for the prevention and treatment of pathological circumstances including neurological disorders (66, 67). Multiple lines of evidence suggest that anthocyanins may have neuroprotective and anti-neuroinflammatory activities that result in improving neural function (68). Neuroinflammation defines specific processes related to the trafficking of immune cells in the central nervous system, which leads to a pathological condition by affecting certain pathways. During the neuroinflammatory process, activation of microglia and astrocytes can cause proinflammatory cytokines to be released and, in turn, activate a second level of inflammatory signaling pathways like nuclear factor-kappa B (NF-κB) (69, 70). Thus, oxidative stress and neuroinflammation can disrupt normal brain function (71). It is suggested that increased generation of reactive oxygen species (ROS) may trigger oxidative injury, cellular damage, mitochondrial dysfunction, and impaired deoxyribonucleic acid repair system which are detrimental factors for neurological function (72, 73). Polyphenols, including anthocyanins, can prevent neuroinflammation, protect neurons against neurotoxin-induced damage, and promote cognitive performance, learning, memory, and neuron survival through their anti-inflammatory and antioxidant activities (74–76). In this regard, Poulose et al. demonstrated that anthocyanins protect the microglial cells subjected to lipopolysaccharide (LPS), a bacterial endotoxin, against neuroinflammation by preventing the activation of p38 and NF-κB and reducing proinflammatory factors such as cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) (77). These findings are consistent with another study in which anthocyanins prevented the up-regulation of inflammatory pathways including Phosphoinositide 3-kinase (PI3K)/AKT, NF-κB, and mitogen-activated protein kinases (MAPKs) in microglial cells, decreasing the generation of pro-inflammatory factors, such as TNF-α, nitric oxide (NO), interleukin (IL)-1β, and prostaglandin E2 (PGE2) (78).

It is noteworthy that the relatively low bioavailability of anthocyanins in the brain may limit their efficacy. Indeed, low concentrations of circulating anthocyanins are considered to be due to the metabolism by gut microbiota to produce different phenolic acid and aldehyde metabolites (79). Some studies indicated that protocatechuic acid (PA), a key anthocyanin metabolite, is a neuroprotective factor through anti-inflammatory and antioxidant features (79, 80).

Cruciferous vegetables including kale, cabbage, Brussels sprouts, horseradish, cauliflower, radish, turnips, and broccoli sprouts are also identified as one of the main components in the ND (81). These vegetables contain a wide variety of nutrients such as protein, carbohydrate, vitamins, minerals, phytochemicals (Tannins, flavonoids, anthocyanins, and carotenoids), phytosterols, and non-nutritive metabolites such as nitrogen-containing compounds and sulfur compounds (glucosinolates and S-methyl cysteine sulfoxide) (82). Several studies have examined the health-promoting effects of cruciferous vegetables in humans and showed that higher consumption of these vegetables is related to a reduced risk of several chronic disorders (83). Besides phytochemicals, the beneficial health characteristics of these vegetables are mainly related to the functions of glucosinolates. In case of plant tissue damage, glucosinolates are hydrolyzed by enzymatic activity, and metabolites such as isothiocyanate, nitriles, and thiocyanates are formed. Also, glucosinolates hydrolysis can occur by intestinal microbiota (84, 85). Cruciferous vegetables, due to their glucosinolates and other metabolites, exhibit several biological properties related to neurological and psychiatric conditions (86, 87). Several studies have provided mechanistic insight into the advantageous effects of glucosinolates on brain health through modulating the hypothalamic–pituitary–adrenal axis, reducing neuroinflammation, oxidative stress, beta-amyloid, and tau production, inhibiting DNA methyltransferases, and increasing brain-derived neurotrophic factor and cellular lifespan (88–90). In a clinical study, daily oral administration of isothiocyanate sulforaphane increased peripheral and brain glutathione, an antioxidant, in healthy human subjects (91). In addition, Ghazizadeh-Hashemi et al. showed that a 6-week sulforaphane administration safely decreased depressive symptoms in patients with a history of cardiac interventions and presence of mild to moderate depression (92). Although, a variety of animal model studies has reported a good effectiveness of sulforaphane interventions for psychiatric and neurodegenerative disorders such as depression, anxiety, schizophrenia, cognitive function, learning and memory, multiple sclerosis, and AD (86, 93–96). Therefore, considering that the positive impacts of cruciferous vegetables and their metabolites are mainly associated with antioxidant and anti-inflammatory mechanisms, the ND may also have beneficial outcomes on neurological function.

Apples and pears are widely consumed in the Nordic regions and are generally recognized as healthy food sources (97). Some studies demonstrated that apples are a good source of antioxidants with various phytochemical compounds. The main phytochemicals in apples are flavonoids (including quercetins, catechin, epicatechin, and proanthocyanidins) and phenolic acids (including p-coumaric acid, chlorogenic acid, and caffeic acid) (97). Quercetin, (3,5,7,3′,4′-pentahydroxyflavone), plays a principal neuroprotective role by inhibiting the proinflammatory mediators that are released by glial cells. Indeed, it is a strong scavenger of free radicals such as ROS and reactive nitrogen species (98). It has been proposed that quercetin prevents neuroinflammation by inhibiting the production of NO in glial cells, which further inhibits the NF-κB signaling pathway and prevents inflammation-related neuronal damage (99). Similarly, it ameliorated activated astrocytes which mediate the generation of ROS and cytokines and further influence neuronal cells and degeneration (100). Most importantly, quercetin may protect the neuronal cells against amyloid beta peptide toxicity by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)- antioxidant response elements (ARE) pathway (101). Activation of the Nrf2-ARE signaling pathway promotes neuroprotection against oxidative injury and cell death (102). Another area of interest regarding the neuroprotective mechanisms provided by quercetin is sirtuins. Quercetin has been shown to activate sirtuin-1, which leads to the protection of cells from apoptosis (101).

The ND is characterized by a high content in whole grain cereals versus refined grains. Whole wheat, oat, rye, and barley are among the main food sources of carbohydrates and other nutrients such as dietary fibers, minerals, and vitamins in the Scandinavian nations. It has been reported that whole-grain cereals are high in phytochemicals such as phytosterols, phenolic acid, and β-glucans which are responsible for the high antioxidant properties (103). A Finnish study revealed that whole-grain consumption was very high among the subjects in Finland with the lowest quartile median consumption (79 g/day), which was higher than the highest quintile mean consumption (45.6 g/day) found in the US population (32). There is ample evidence to support that whole grain cereals have health-benefits effects (30). Mounting evidence demonstrated that whole-grain cereals are good sources of fermentable carbohydrates, including resistant starch, dietary fibers, and oligosaccharides, that cannot usually be broken down by the digestive enzymes of humans. However, the gut microflora selectively breaks down and ferments them into gases and short-chain fatty acids (SCFAs) (104). SCFAs are absorbed and utilized by the gastrointestinal epithelial cells, as well as beneficial bacteria such as lactobacilli and bifidobacterial; therefore improving the gut microbial community, decreasing the gut pH, and enhancing the immunity of the body (105). Extensive research efforts have indicated that an appropriate increase in whole-grain intake (barley and oats) can enhance the growth of probiotics and enhance intestinal and distal organ functions (106, 107). On the other hand, evidence is emerging supporting the role of intestinal microbiota in the brain function by the gut-brain axis, thereby regulating neurological activities such as behavior, cognitive function, and mood (108, 109). Gut-brain axis involves a complex structure of immunological, neural, and endocrinological factors, that can be an important target for manipulating brain health (109). A cross-sectional study demonstrated an inverse relationship between fiber supplementation and depressive symptoms (110). However, there was no significant association in Gopinath et al. study (111). Overall, there are complex mechanistic processes involved in the impacts of dietary fiber-derived whole grains on brain health. Metabolites from bacterial fermentation, such as SCFAs, may play a variety of regulatory roles including histone acetylation, signaling through G protein-coupled receptors, and affect the host’s immune system by altering the circulating levels of inflammatory mediators and reducing neuroinflammation (112). In animal models of endotoxin-induced sickness behavior, pectin as the only source of fiber decreased brain TNF-α and IL-1β (113).

Moreover, gut microbiota modulates serotonin concentration, a neurotransmitter, and the metabolism of tryptophan, which is often targeted by anti-depressant medications in the central nervous system (114). Butyrate, one of the SCFAs, can increase the transcripts of brain-derived neurotrophic factor (BDNF), an important molecule for maintaining the integrity of neurons and cognitive function, in the brain (115). It is worth noting that the gut microbiome may directly or indirectly affect the generation of neurotransmitters, such as dopamine, γ-aminobutyric acid (GABA), and acetylcholine which modulate cognition and mood status (109). The potential action mechanisms of the ND on the gut-brain axis are shown in Figure 3.

Besides fibers, a growing body of evidence has revealed that whole-grain cereals are rich in a variety of phytochemicals, including phytic acid, flavonoids, terpenes, coumarins, and phenolic compounds, which have various physiological activities, including hypotensive, antibacterial, anti-hyperglycemia, immunomodulation, antioxidant, anti-tumor, anti-inflammation, and anti-aging (103). These compounds are documented to exert antioxidant and anti-inflammatory activities, resulting in a neuroprotective effect (103). It is worth noting that studies on animals have shown that diets high in carbohydrates and low in protein could lead to the longest lifespan and improved cognition. It may be concluded that the quality of dietary carbohydrates is more important than its quantity on nerve function and brain health (116, 117).

Legumes are nutritionally valuable, providing several nutritious components including proteins with essential amino acids, minerals, vitamins, dietary fibers, complex carbohydrates, unsaturated fats, and non-nutritional compounds such as alkaloids, isoflavone, phytic acid, phenolic compounds (tannins), and saponins (113). Dietary isoflavones derived from legumes may have beneficial effects on brain health, receiving new attention regarding neuroprotective properties (118). These compounds are classified as phytoestrogens which are most extensively investigated. Isoflavones can mimic the transcriptional effects of estrogen via binding to estrogen-receptor beta (ERβ), mediating estrogen action, and thereby inhibiting apoptotic cell death (119). Estrogen and its mimics modulate synaptic plasticity, neuronal survival and growth, and brain function through an estrogen receptor-mediated pathway, and subsequently regulation of gene transcription and second messenger systems (120).

Moreover, the antioxidant action of isoflavones has been suggested to be involved in the presumed effect of legumes on brain health. These compounds afford protection against neuroinflammation by ameliorating oxidative damage, upregulating endogenous antioxidant signaling pathways, and protecting the integrity of the mitochondria (119, 121). These antioxidant activities may be attributed to the inhibition of the NF-κB signaling pathway (121). In this regard, some studies demonstrated that isoflavones prevent microglial activation and inflammation (122, 123). In vitro studies have shown that isoflavone treatment exhibited protection against apoptosis via regulating the antiapoptotic bcl-2 protein suppression and modulating cell survival signaling (120, 121). Other protective effects of dietary isoflavones on brain health can mediate by reductions in proapoptotic proteins such as Bax and Bad, and modulation of kinase signaling (119).

Fish, especially fatty fish, and seafood are one of the natural components in the ND, with high amounts of polyunsaturated fatty acids (PUFAs) containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In addition, these food sources contain many other valuable nutrients such as vitamins and minerals (30). It was commonly suggested that the major dietary components of fish are DHA and EPA, which are the main building blocks for nerve cell membranes and play a crucial role in proper brain development and function, neurotransmission, and ion channel modulation, and thus are effective in neuroprotection. Some studies reported that there is a relationship between the reduction of omega-3 PUFA concentration in the blood serum and erythrocyte membranes with several neuropsychiatric disorders such as depression, schizophrenia and also dyspraxia, dyslexia, autism, and attention-deficit hyperactivity disorder (ADHD) (124–126). Omega-3 PUFAs have several mechanisms of action in the cerebral vascular system and brain that could improve brain function (127). First, they seem to attenuate inflammation by reducing the production of pro-inflammatory cytokines from arachidonic acid. Omega-3 PUFAs compete with arachidonic acid for incorporation into phospholipid membranes in the cyclooxygenase pathway by preventing the generation of proinflammatory eicosanoids, including prostaglandin E2 and thromboxane B2. EPA and DHA can also prevent the secretion of other pro-inflammatory mediators including interleukins (IL-1, IL-1β, IL-2, IL-6), TNF-α, and interferon-gamma (IFN-γ). Other anti-inflammatory mechanisms are the reduction of T-cell proliferation and inhibition of leukocyte migration. Considering that inflammation is involved in the pathophysiology of neurological disorders, these fatty acids might exert neuroprotective properties through their anti-inflammatory effects (127–129). Second, long-chain omega-3 fatty acids decrease cardiovascular risk factors, including hypertriglyceridemia, and enhance the blood flow in the brain, thus reducing cerebrovascular disease by modulating risk factors (127).

Moreover, a growing body of evidence suggests that omega-3 fatty acids affect the receptor function, the neurotransmitter level, and its metabolism. In this regard, some studies indicated that these fatty acids are related to the activity of the serotoninergic system. There is a relationship between low DHA levels and low concentrations of 5-hydroxyindolacetic acid (5-HIAA), the main metabolite of serotonin, in the cerebrospinal fluid, observed in people suffering from depression and schizophrenia. This can imply that low levels of omega-3 fatty acids are associated with impaired serotonergic neurotransmission (130, 131). DHA induces BDNF synthesis, thus sustaining the life of neurons. In addition, PUFAs deficiency may impair the release and uptake of neurotransmitters, enzymatic processes, and function of ion and receptor channels such as dopaminergic, GABAergic, and cholinergic in nervous system cells, contributing to the development of psychiatric disorders including depression, anxiety, and aggression (126, 132). Some studies suggest that low consumption of fish is associated with increased prevalence of depression (129).

It is also known that the consumption of omega-3 PUFAs is recommended for the prevention of AD. Consuming fish once a week decreases the risk of AD by 60%. EPA and DHA can reduce amyloid-β production and its accumulation in plaques, and improve its clearance (127). In the Cardiovascular Health and Cognition study, consumption of fatty fish (≥ 2 servings per week) reduced the incidence of dementia by 28% and reduced the risk of AD by 41% (133).

Rapeseed oil is regarded to be a key oilseed product in Nordic countries. It is characterized by a low level of saturated fatty acids (7%), and substantial amounts of mono- and polyunsaturated fatty acids such as alpha-linolenic acid, linoleic acid, and oleic acid (134). These fatty acids are known as neuroactive molecules (135). Oleic acid (18:1ω9 monounsaturated fatty acid) is critical for the survival of neural stem cells, which are the source of newborn neurons in the brain and are involved in mood, memory, learning, and stress response. In a rodent model study, oleic acid bound to the orphan nuclear receptor TLX/NR2E1 (nuclear receptor subfamily 2, group E, member 1), converted it from a transcriptional repressor to a transcriptional activator of cell-cycle and neurogenesis genes and induced neurogenesis and brain development (136). Similar beneficial effects were also shown in another animal study, in which oleic acid administration demonstrated its neuroprotective effects in transient and permanent focal cerebral ischemia (137). It is believed that oleic acid is associated with the onset of neurodegeneration disease through anti-inflammatory and vascular activities (138).

Moreover, multiple regression analysis of cohort study data revealed that daily consumption of oleic acid has a significantly positive effect on cognitive decline in community-dwelling Japanese elderly subjects (139). Certain dietary patterns, such as MD which contains high amounts of oleic acid, have been strongly associated with protection against age-related cognitive decline (140–142). Therefore, it is highly likely that rapeseed oil, as a source of oleic acid and PUFAs, may be a beneficial food that is closely related to neurological disorders.

Future directions should focus on precise dietary patterns and their applications in brain health. The neurological benefits of ND are not very well investigated. On the other hand, considering the different designs of studies and limitations in the number of studies, we chose the narrative approach for the present review. There is a need to investigate the randomized trial in placebo versus Nordic diet group in different populations. Overall, more and long-term human studies are needed to confirm the neuroprotective effects of the ND.