Introduction

Inflammation is a pivotal component of innate immunity in response to endogenous and exogenous harmful stimuli (i.e., toxic chemicals, environmental agents, trauma, and pathogens/viral infection), which is physiologically challenged as a defense mechanism for injury removal and wound healing processes [1].

Based on timing and pathological features, inflammation can be acute and chronic [2]. Acute inflammation is usually of short duration (minutes to days) consisting of the migration of lymphocytes/neutrophils and macrophages to the inflammatory site, which stimulate the release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and high motility group box-1 (HMGB-1) as well as cell aggregation and enzyme breakdown [3]. Moreover, the activation of NOD-like receptors (NLRs) such as NLRP3, NLRP1, and NLRC4 results in the recruitment of a highly regulated protein complex (known as inflammasome), whose activation initiates downstream inflammatory cytokine production, mainly interleukin 1 beta (IL-1β) and interleukin 18 (IL-18) in response to cellular stress [4]. Other intermediaries encompass chemokines, lipid mediators, acute-phase proteins such as C-reactive protein (CRP), transcriptional factors including the nuclear factor kappa B (NF-κB), and major immune cell types [5].

However, uncontrolled acute inflammation may become a permanent condition leading to expanded tissue damage, hemodynamic changes, and organ failure [6]. In fact, chronic inflammation has been linked to the development of non-communicable diseases such as obesity and associated comorbidities [7]. In this regard, obesity leads to abnormal fat accumulation in adipocytes, immune cell infiltration, and pro-inflammatory milieu that disrupt the insulin signaling cascade inducing insulin resistance [8]. Besides, inflammation and oxidative stress interactions are critical to understand the physiopathology of obesity, involving impairments of endoplasmic reticulum functions, hypoxia in the adipose tissue, mitochondrial alterations, and reactive oxygen species overproduction [9]. Furthermore, gut microbiota seems to be implicated in the development of obesity-related low-grade inflammation involving lipopolysaccharides translocation and toll-like receptor 4 (TLR-4) binding, which trigger a state of blood endotoxemia [10]. The resulting unresolved immune activation not only affects local tissues, but also systemic physiology that is termed meta-inflammation [11].

Therefore, it is relevant to identify the triggers that activate pro-inflammatory cascades in order to identify potential targets as well as implement precision intervention strategies for health care [12]. In this context, cumulative population-based evidence supports the role of nutrition on inflammatory pathways [13]. In this critical review, the effects and eventual mediation of different nutritional factors on inflammation are discussed, including specific nutrients (types of carbohydrates, protein sources, structural fatty acids, micronutrients, and trace elements) and bioactive compounds (polyphenols); staple-characterized dietary patterns (i.e., Western, Mediterranean, and Nordic diets); therapeutic diets (i.e., DASH approach); common culinary ingredients (species and herbs); and chrononutrition features (Fig. 1). Moreover, the potential of prescribing personalized anti-inflammatory diets based on social, phenotypical, clinical, genetic/epigenetic, and metabolic/metabolomic characteristics with a precision medicine scope is postulated (Fig. 2).

Fig. 1
figure 1

Nutritional factors associated with inflammatory outcomes in humans. DASH, Dietary Approaches to Stop Hypertension; EGCG, epigallocatechin-3-gallate; Med-diet, Mediterranean diet; MUFA, monounsaturated fatty acids; PREDIMED, Prevención con Dieta Mediterránea; PUFA, polyunsaturated fatty acids; SEAD, Southern European Atlantic Diet; SFA, saturated fatty acids; TFA, trans fatty acids; TMexD, traditional Mexican diet

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Fig. 2
figure 2

Precision information for the prescription of personalized anti-inflammatory nutritional strategies

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The Role of Nutrition on Inflammation

Macronutrients

Total Carbohydrates

Dietary carbohydrates exert differential effects on health depending on quantity and quality features [14]. Interestingly, a low-carbohydrate diet (20% of total energy) significantly improved the subclinical inflammatory state (lower serum levels of IL-1Ra and IL-6) in diabetic patients [15]. Notably, the adherence to a low-carbohydrate diet (35% of total energy) reduced the levels of inflammatory markers in women with obesity [16]. Also, it was found an overall favorable effect of a low-carbohydrate diet (≤ 30 g/day) on inflammation in subjects with severe obesity [17]. Additionally, a very low carbohydrate diet (12% of total energy) resulted in relevant reductions in inflammation compared to a low-fat diet (24% of total energy), as reported elsewhere [18].

Glycemic Index

The glycemic index (GI) has been devised to physiologically assess the carbohydrate quality from different foods based on effects on postprandial plasma glucose concentrations [19]. Interestingly, a high-GI diet (based on cooked vermicelli pasta, GI = 35) significantly increased the activation rates of NF-κB in mononuclear cells in lean healthy subjects [20]. Indeed, the negative metabolic and inflammatory responses induced by a high-GI diet (GI > 70) were counteracted by a low-GI diet (GI < 55) in diabetic patients [21]. Furthermore, findings from the DIOGenes trial revealed that low-GI carbohydrates (15 points of difference regarding high-GI carbohydrates) may reduce low-grade inflammation in subjects with overweight or obesity following a weight maintenance diet after weight loss [22].

Fiber

Dietary fiber may provide health benefits involving some immunological mechanisms [23]. Accordingly, fiber intake equal or more than 15 g/1000 kcal has been associated with decreased blood CRP levels in diabetic patients [24]. Accordingly, a randomized intervention trial demonstrated that fiber intake (30 g/day) from a diet naturally rich in fiber or from a supplement can substantially reduce the circulating levels of CRP in lean normotensive participants [25]. Moreover, significant inverse linear associations were detected between dietary fiber intake (mean 16.8 g/day) and CRP serum concentrations in middle age adults [26].

Total Fat

Dietary fat elicit a number of essential functions in the organism; however, excessive fat consumption may lead to obesity and related low-grade inflammatory processes [27]. Indeed, clinical evidence indicates that high-fat diets (i.e., nearly 75% of total energy) cause overproduction of circulating free fatty acids and systemic inflammation [28]. Consistently, a low-fat diet (25% of energy needs) was associated with lower plasma IL-6 levels in diabetic patients [29].

Saturated Fatty Acids

There is increasing evidence concerning the fact that dietary saturated fatty acids (SFAs) act as an important link between obesity and inflammation [30]. Interestingly, subjects consuming more than 10% energy as saturated dietary fat had increased serum levels of CRP compared to subjects having a normal saturated fat intake (< 7% of caloric intake) in young Asian Indians [31]. Likewise, ingestion of SFA (100 mL of dairy cream with 70% saturated fat content) resulted in lipid-induced increases in plasma CRP in women independently of obesity status [32].

Monounsaturated Fatty Acids

Monounsaturated fatty acids (MUFAs) are assumed as a healthy type of fat, being the oleic acid (OA) the most commonly consumed MUFA in daily nutrition [33]. In this context, a cross-sectional epidemiologic study in Japanese population reported a significant inverse relationship between the intake of OA (mean 6.94% of total energy) and serum CRP concentrations [34]. Further controlled trials with different doses of MUFA for the treatment of inflammatory features are warranted.

Polyunsaturated Fatty Acids

In the last years, a plethora of evidence has supported the beneficial effects of polyunsaturated fatty acids (PUFAs) in the prevention of cardiovascular and other chronic diseases with an inflammatory basis [35]. In this context, the intakes of the n-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were inversely associated with plasma levels of soluble TNF receptors 1 and 2 in healthy individuals [36]. Moreover, total dietary n-3 PUFAs inversely correlated with blood levels of CRP and IL-6 in women [37].

Additionally, some clinical trials have evaluated the effects of prescribing diets high in PUFA or through PUFA supplementation on inflammatory outcomes. For instance, fish oil supplementation (38.2 g/day EPA + DHA during 90 days) lowered the blood levels of pro-inflammatory markers in hypertensive patients [38]. Similarly, healthy young adults receiving n-3 PUFA (2.5 g/day, 2085 mg EPA and 348 mg DHA) for 12 weeks underwent a 14% decrease in serum IL-6 levels [39]. Likewise, low (1.25 g/day) or high (2.5 g/day) doses of n-3 PUFA supplementation for 4 months reduced inflammation responses (specifically serum IL-6 and TNF-α concentrations) in overweight adults [40].

Trans Fatty Acids

Trans fatty acids (TFAs) are mainly industrially formed by the hydrogenation of vegetable oils or from ruminant-derived foods including dairy products and meats [41]. TFA intake has been positively associated with plasma biomarkers of inflammation (including CRP, VCAM-1, E-selectin) in women [42]. In this same population, the consumption of TFA was positively associated with the plasma levels of soluble TNF receptors 1 and 2, mainly in women with higher body mass index [43]. Furthermore, serum CRP concentrations were elevated after TFA consumption (8% of total fat) in men [44].

Dietary Cholesterol

Excessive cholesterol may have deleterious effects on health including some processes affecting inflammation status [45]. For example, highest quartile of serum CRP concentrations (5.9 mg/L) was associated with higher intake of dietary cholesterol (189 mg/day) among Iranian adults [46]. Likewise, in a large representative Middle East population, positive correlations between dietary cholesterol and plasma CRP levels were found [47].

Protein Quantity and Quality

Both the quantity and quality of dietary protein are main determinants of nutritional values and body/endocrine homeostasis [48]. Among participants of the Framingham Heart Study Offspring cohort, dietary protein intake (particularly from plant sources) was inversely associated with serum markers of inflammation such as IL-6 and CRP [49]. Moreover, consuming high (30% of total energy) or low (10% of total energy) protein diets resulted in reduced blood CRP concentrations in morbidly obese individuals [50].

Regarding protein sources, diets characterized by higher intakes of animal protein (high levels of fatty and processed meats) were positively associated with certain blood pro-inflammatory markers such as CRP, IL-6, TNF-a, IL-8, serum amyloid A, and glycoprotein acetylation [51]. Furthermore, findings from the RESMENA dietary study (30% energy from protein) revealed positive associations between animal and meat protein intakes and inflammation, whereas vegetable- or fish-derived proteins had no significant influence on inflammatory status [52].

Micronutrients

Vitamins

Longitudinal and observational studies have shown some associations between dietary vitamin intakes and inflammatory features. For instance, consumption of vitamins C and E or carotene were inversely associated with the probability of having serum CRP concentrations > 3 mg/L in American adults [53]. In the cross-sectional KORA study, dose–response analyses revealed that participants, who regularly ingested more than 78 mg vitamin E/day, had 22% lower serum CRP levels than subjects who were not exposed to any extra vitamin E sources [54].

In addition, the intakes of dietary supplements containing vitamin E and C as well as B-complex vitamins (B1, B2, B3, B5, B6, B9, and B12) were associated with lower blood CRP levels in women [55]. Moreover, subjects in the upper tertile of changes in dietary vitamin K1 (phylloquinone) intake (after 1-year of follow-up) showed a greater reduction in IL-6 and TNF-α plasma concentrations than those in the lowest tertile group [56]. Also, dietary B5 vitamin intake was inversely related to serum CRP concentrations in healthy Korean adults [57]. Furthermore, participants who consumed > 310 mg/day of dietary choline (commonly grouped within the B-complex vitamins) had lower blood concentrations of CRP, IL-6, and TNF-α in healthy adults [58]. Findings of clinical trials exploring the impact of vitamins on inflammation status are systematically summarized (Table 1). Some studies have found relevant benefits on lowering inflammation after vitamin supplementation.

Table 1 Clinical trials analyzing the anti-inflammatory effects of certain vitamins and bioactive compounds
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Minerals and Trace Elements

Minerals and trace elements are essential for structural, immunological, and metabolic functions in the human organism [93]. In this regard, high magnesium consumption was related to lower plasma concentrations of potential markers of systemic inflammation (CRP, sTNF-R2, and IL-6) in postmenopausal women [94]. Similarly, magnesium intake from dietary sources was found to be inversely correlated with plasma IL-6 in women from the Nurses’ Health Study cohort [95]. Likewise, a nested case–control study reported an opposite association concerning dietary manganese and circulating levels of serum pro-inflammatory cytokines in postmenopausal women [96]. Also, changes in lymphocyte proliferation and IL-2R expression have been reported to be early markers of mild zinc dietary deficiency in healthy men [97]. In addition, dietary copper intake has been directly associated with blood CRP concentrations in adults [98]. In turn, iron deficit may be exacerbated by the effects of obesity-related inflammation on gut iron absorption [99]. Furthermore, main outcomes regarding the anti-inflammatory effects of supplementation with certain minerals on humans are shown (Table 2).

Table 2 Clinical trials analyzing the anti-inflammatory effects of certain minerals
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Bioactive Compounds

Polyphenols

Polyphenols are a large family of bioactive molecules widely occurring in plant-based foods, with potent antioxidant and anti-inflammatory properties [136]. In this context, it was reported that total flavonoid intake was inversely associated with serum CRP concentration in American adults [137]. Also, inverse relationships between flavanone consumption and blood IL-6 concentrations were reported in a multiethnic cohort [138]. Likewise, higher isoflavone intake (highest quartile = 1.61–78.8 mg/day) was related to lower plasma CRP in healthy premenopausal women [139]. Besides, lower serum levels of IL-8 were found among women showing high intakes of flavones, flavanones, and total flavonoids (highest quintiles = 264 ng/L, 273 ng/L, and 276 ng/L, respectively) [140]. Moreover, elevated total flavonoids intake and tea consumption inversely correlated with CRP levels in Taiwanese [141]. Of note, a number of randomized clinical trials have tested the anti-inflammatory potential of several polyphenols, whose results are summarized (Table 3).

Table 3 Clinical trials analyzing the anti-inflammatory effects of certain polyphenols
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Specific Foods

Red Meat

Concerning implications on inflammation, greater total (median 54 g/day), unprocessed (median 47 g/day), and processed red meat intakes (median 4 g/day) have been associated with unfavorable plasma concentrations of inflammatory biomarkers (including CRP and ferritin) in women [168]. Within the Multiethnic Cohort Study, red and processed meat consumption positively correlated with serum CRP levels [169]. Likewise, the consumption of processed meat was associated with increased levels of serum CRP (difference of 38% for each 50 g/day higher intake) in British adults [170]. In adjusted models, red meat consumption was significantly associated with blood CRP in a large American sample [171].

Dairy Products

In a cross-sectional study in Brazilians, increased yogurt consumption (median 10 g/day) appeared to exert an anti-inflammatory effect, whereas cheese consumption (median 10.7 g/day) could have potentiated a pro-inflammatory status [172]. In normal-weight adolescents, total dairy product and milk intakes were inversely associated with the serum concentrations of IL-6 [173]. Also, findings from the ATTICA study showed lower blood levels of CRP, IL-6, and TNF-α among individuals weekly consuming between 11 and 14 servings of dairy products compared to those consuming fewer than 8 servings per week [174].

Fish

Findings from the ATTICA study revealed independent associations between habitual fish consumption (> 300 g of fish per week) and lower inflammatory marker levels among healthy adults, including reduced CRP, IL-6, TNF-a, serum amyloid A, and white blood cell counts [175]. During a 6-year follow-up, fish consumption (about 100 g/week) decreased endothelial dysfunction and low-grade inflammation in healthy adults [176]. Furthermore, a high frequency of fish intake was associated with lower peripheral white blood cell counts (a marker of chronic inflammation) in an apparently healthy Japanese population [177]. In fact, the neutrophil/lymphocyte ratio (a marker of systemic inflammation) significantly decreased as the weekly frequency of fish intake (0 day, 1–2 days, 3–4 days, or 5–7 days) increased [178].

Edible Insects

In recent years, edible insects are being recognized as high-value food products with anti-inflammatory and antioxidant properties [179]. For example, cricket consumption (25 g/day) was associated with reduced systemic inflammation via microbiota modulation in healthy adults [180]. However, more research in humans is required to confirm these findings in order to recommend the habitual consumption of edible insects as an anti-inflammatory therapy.

Fruits and Vegetables

Inverse associations were found between the intakes of fruits and vegetables and serum CRP levels in Iranian females [181]. Besides, Chinese women consuming high amounts of cruciferous vegetables (highest quintile > 140.6 g/day) showed decreased circulating levels of TNF-α, IL-1β, and IL-6 [182]. In a randomized crossover trial, the consumption of cruciferous vegetables (14 g/kg body weight) during 14 days consistently reduced circulating IL-6 in in healthy young adults [183].

Oilseeds and Extra Virgin Olive Oil

In the multi-ethnic study of atherosclerosis, frequent nut and seed consumption (especially five or more times/week) was associated with lower levels of inflammatory markers, including IL-6 and CRP [184]. Moreover, in two large cohorts of Americans, subjects with a nut intake of five or more times/week had significantly lower blood concentrations of CRP and IL-6 compared to individuals in the frequency categories of never or almost never [185]. Likewise, a systematic review and meta-analysis of randomized controlled trials revealed that intakes of flaxseed and associated nutritional derivatives systematically reduced circulating CRP levels in obese subjects [186]. Using the same approach, acute high-oleic peanut consumption systematically led to stronger moderation of postprandial TNF-α concentrations in overweight/obese men [187].

Additionally, it has been shown that the incorporation of almonds (56 g/day during 4 weeks) into a healthy diet could improve inflammation and oxidative stress in Chinese diabetic patients [188]. A randomized trial also found that the consumption of almonds (10–20% isoenergetic replacement of control diet with almonds for 4 weeks) lowered serum CRP levels in healthy adults [189]. Indeed, plasma levels of TNF-α and IL-6 decreased after almond feeding (56 g/day for 90 days) in adolescents and young adults [190].

Furthermore, it has been reported that a daily dose of 50 mL of extra virgin olive oil (EVOO), administered over two periods of 3 weeks, decreased the plasma levels of IL-6 and CRP in stable coronary heart disease patients [191]. Besides, EVOO (50 mL) exerted acute postprandial anti-inflammatory and antioxidant effects in normolipemic, healthy subjects [192].

Cereals and Whole Grains

Interestingly, the intake of cereal fiber was inversely associated with lower blood levels of CRP and TNF-R2 in diabetic women [193]. Moreover, concomitant reductions in serum TNF-α and increased plasma IL-10 were found after the consumption of whole-grain wheat (70 g/day during 8 weeks) in subjects with overweight and obesity [194]. In addition, findings from the GRAANDIOOS study showed that whole-grain wheat consumption (98 g/day for 12 weeks) may promote liver and inflammatory resilience in subjects with overweight/obesity and mild hypercholesterolemia [195].

Legumes

Soy food consumption has been inversely related to circulating levels of inflammatory markers such as IL-6, TNFα, and soluble TNF receptors 1 and 2 in middle-aged Chinese women [196]. Consistently, a 6-week nutritional trial with a legume-enriched diet (a total of 24 packs of 65 g were consumed during the all the intervention phase) significantly reduced CRP concentrations in diabetic patients compared with a habitual diet [197]. Moreover, a legume-based hypocaloric diet (160–235 g/day for 8 weeks) consistently reduced pro-inflammatory status and improved metabolic features in overweight/obese subjects [198].

Green Tea and Coffee

In obese women, green tea extract (450 mg/day) supplementation during 8 weeks improved oxidative stress biomarkers and reduced IL-6 circulating levels [199]. Also, green tea consumption (379 mg/day) by 3 months reduced serum CRP and TNF-α concentration in obese, hypertensive patients [200]. Furthermore, high coffee consumption (8 cups/day) exerted beneficial effects on subclinical inflammation in habitual coffee drinkers [201]. Consistently, coffee consumption was inversely associated with markers of inflammation and endothelial dysfunction in healthy and diabetic women [202]. Among older non-Hispanic Whites, heavy coffee drinkers (equal or more than 2.5 cups/day) presented lower systemic inflammation [203]. On the other hand, analyses from the ATTICA study reported an increase on inflammation markers (including IL-6, TNF-α, and CRP) after moderate-to-high coffee consumption (> 200 mL coffee/d), emphasizing the importance of the dose in outcomes [204].

Dark Chocolate

Available evidence suggests that regular consumption of dark may reduce inflammation, especially in consumers of up to 1 serving (20 g) of dark chocolate every 3 days [205]. In a randomized parallel clinical trial, diabetic patients, who received dark chocolate (30 g of 84% dark chocolate during 8 weeks) along with a healthy lifestyle, had lower levels of inflammatory markers (CRP, TNF-α, and IL-6) compared with those subjects who only followed general lifestyle guidelines [206]. Indeed, acute dark chocolate intake (50 g) elicited anti-inflammatory outcomes both by increasing IL-10 expression and by attenuating the intracellular pro-inflammatory stress response [207]. Moreover, healthy women presented lower blood levels of CRP after the ingestion of dark chocolate (100 g per day during one week), which was not detected in men [208].

Spices and Culinary Ingredients

Over the past several decades, several investigations have ascertained the efficacious role of spices and herbs in preventing and combating various chronic diseases [209]. The diverse range of health properties of these culinary ingredients are attributed to bioactive constituents such as sulfur-containing molecules, tannins, alkaloids, and phenolic diterpenes, with potential anti-inflammatory properties [210]. Findings of clinical trials exploring the impact of spices on inflammation status are summarized (Table 4).

Table 4 Clinical trials analyzing the anti-inflammatory effects of certain spices and culinary ingredients
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Probiotics, Prebiotics, Synbiotics, and Postbiotics

Probiotics, prebiotics, and synbiotics are either beneficial microorganisms, substrates (polysaccharides and oligosaccharides), or combinations that eventually may also alleviate inflammatory symptoms [240]. In diabetic patients, probiotic and synbiotic supplementation is recommended to decrease inflammatory manifestations by consistently reducing the circulating levels of CRP and TNF-α [241]. Regarding bowel disease, it has been recently reported that the use of probiotics (based on Lactobacillus and Bifidobacterium) and synbiotics can promote anti-inflammatory reactions and balance the intestinal homeostasis [242].

In addition, the anti-inflammatory effects of short-chain fatty acids (nonviable bacterial products known as postbiotics) are mediated by inhibiting the NF-κB pathway, Treg cell differentiation, and pro-inflammatory cytokine blockade in gut epithelial cells [243]. For example, Lactobacillus casei DG and derived postbiotics suppressed IL-8, IL-1α, IL-6, and TLR-4 expression levels in colonic mucosa from patients with irritable bowel syndrome [244].

Dietary Patterns

Traditional Healthy Diets

Overall, plant-based diets have shown to improve the obesity-related inflammation status [245]. Remarkably, the beneficial effect of the vegetarian diet on blood CRP and IL-6 levels was mediated by BMI in North Americans [246]. In addition, a systematic review and meta-analysis revealed that vegetarian-based dietary patterns also lowered immune biomarkers such as fibrinogen and total leukocyte concentrations [247].

A systematic review of observational and intervention trials revealed a beneficial influence of the Nordic diet (based on staple foods from Nordic countries) on low-grade inflammation amelioration [248]. Potential mechanisms include the downregulation of pro-inflammatory genes in individuals with features of the metabolic syndrome, particularly TNFRSF1A and RELA [249].

The Southern European Atlantic Diet (SEAD) is the traditional diet of Northern Portugal and Galicia, Spain, which is characterized by greater intakes of fish, milk, potatoes, fruit, vegetable and olive oil, and red wine [250]. Overall, SEAD adherence has been associated with reduced plasma concentrations of inflammatory markers (predominately CRP) and lowered cardio-metabolic risk [251].

Regarding Asian regions, a healthy Japanese dietary pattern (rich in mushrooms, seaweed, soyabean products and potatoes, vegetables, fish/shellfish, and fruits) seems to exert anti-inflammatory effects and improve mental health in local consumers [252]. Likewise, several herbs from traditional Chinese medicine have shown to suppress pro-inflammatory pathways and control inflammation-associated diseases [253].

Furthermore, the traditional Mexican diet (TMexD) has shown to reduce the risk of systemic inflammation and insulin resistance in women of Mexican descent [254]. Specific foods of the TMexD include maize, beans, chili, squash, tomato, nopal, and onion, which are high in fiber, vitamins, minerals, and capsaicinoids, with potential anti-inflammatory and antioxidant properties [255].

In a pooled cross-sectional study, a Paleolithic diet (based on the consumption of diversity of vegetables and fruits, lean meat, fish, nuts, and sources of calcium) was associated with lower levels of systemic inflammation and oxidative stress in humans [256].

Moreover, the consumption of the DASH eating pattern (characterized by high consumption of fruits and vegetables, low-fat dairy products, and complex carbohydrates) during 6 weeks reduced the circulating levels of CRP among adolescents with metabolic syndrome [257]. In female adults, the DASH diet was cross-sectionally associated with lower serum CRP levels, but not with IL-17A concentrations in Iranians [258]. Quantitative estimations revealed that the DASH diet reduced CRP by 13% after 4 weeks of follow-up [259].

Findings from the PREDIMED trial have shown the anti-inflammatory effect of the Med-diet (rich in vegetables and fruits, fiber, and vitamins C and E) since it downregulates cellular and circulating inflammatory biomarkers involved in atherogenesis development [260]. In this cohort, the Med-Diet reduced the serum CRP and IL-6 levels as well as endothelial and monocytary adhesion molecules and pro-inflammatory chemokines [261]. Additionally, the Med-diet (including EVOO and vegetables) decreased the plasma concentrations of TNFR60 in patients at high cardiovascular risk after 1 year of follow-up [262]. In the long term (3 years), the PREDIMED trial confirmed the anti-inflammatory effect of the Med-diet by decreasing the levels of IL-1β, IL-6, IL-8, and TNF-α compared to a control low-fat diet [263].

Westernized Diets and Ultra-processed/Discretionary Foods

Overall, the adoption of Western-type diets (WTD), with high contents of unhealthy fats, refined grains, sugars, and salt, evokes a state of chronic metabolic inflammation [264]. In this regard, a WTD showed positive associations with markers of inflammation and endothelial dysfunction in women from the Nurses’ Health Study I cohort [265]. Also, a comparable WTD score positively correlated with CRP and IL-6 pro-inflammatory markers among Iranian women [266].

Interestingly, positive associations were found between the consumption of ultra-processed foods (UPF), which contain high amounts of free sugars, total fats, SFA, TFA, and sodium, and serum CRP levels among Brazilian women [267]. Likewise, Brazilian adolescents in the upper tertile of UPF (≥ 30% of total energy) had increased circulating IL-8 concentrations when compared with adolescents in tertile 1 (≤ 15.9% of total energy) of UPF [268].

Furthermore, a poor diet quality (considering habitual discretionary food consumption such as sweets, cakes, soft drinks, and fried potatoes) was associated with increased inflammation measured as plasma CRP and erythrocyte sedimentation rates in Swedish patients with rheumatoid arthritis [269].

Chrononutrition Patterns

Recent progress in the analysis of circadian rhythms and nutrition (referred as “chrononutrition”) has revealed that the time of day when food is consumed may affect metabolic homeostasis and immune function [270]. In this context, a significant association between breakfast skipping and elevated serum CRP concentrations was reported in Chinese adults with poor diet quality [271]. In a randomized controlled crossover trial, breakfast skipping induced a higher activation of the NLRP3 inflammasome in human peripheral blood mononuclear cells and monocytes [272].

Intermittent fasting (IF), where individuals fast on consecutive or alternate days, has improved systemic inflammation in males with obesity [273]. Nevertheless, a transient elevation of biomarkers of macrophage infiltration in adipose tissue (CD40 +) and skeletal muscle (CD163 +) were found after IF in women with overweight or obesity [274].

Available evidence suggests that time-restricted eating (TRE), an alternative chrononutritional approach based on the consolidation of the total calorie intake during the active phase of the day, may modulate a variety of metabolic disease risk factors including exacerbated inflammation [275]. Indeed, it has been postulated that TRE as part of a periodized nutrition plan could be beneficial for reducing inflammation and induce a protective effect on some components of the immune system [276].

Interestingly, greater reductions in blood CRP levels were found in patients with metabolic syndrome after following an alternate day fasting (ADF), which consists of a “fast day,” where caloric intake is limited, alternating with a “feed day,” where food is consumed ad libitum [277]. Moreover, ADF reduced the plasma levels of sICAM-1 (an age-associated inflammatory marker) in healthy non-obese subjects [278].

Additionally, it has been reported that late eating, which refers to delay in the timing of meals (commonly the main meal of the day or the dinner) may increase the risk for developing cardiometabolic diseases [279]. In fact, late eating was associated with abdominal obesity, inflammatory biomarkers such as IL-6 and CRP, and circadian-related disturbances in children [280].

Personalized Anti-inflammatory Nutritional Strategies

The integrative analysis of precision variables (age, sex, body phenotype, habitual dietary intake, physical activity levels, and lifestyle) together with personalized issues (genetic background, epigenetic signatures, microbiota composition, gene expression profiles, and metabolomic fingerprints) may contribute to the prescription of more personalized treatments seeking to improve the nutritional and medical management of inflammation (Fig. 2). For example, there is evidence that genetic variation may predispose to inflammatory conditions through interactions with environmental factors, such as diet, modulating the individual susceptibility to developing inflammation-related chronic and acute diseases [281]. Also, epigenetic signatures (including DNA methylation, miRNA expression, and histone modifications) play a fundamental role in inflammatory gene transcription [282]. Of note, a microbiota-based regression model has been able to predict the obesity-related inflammatory status in humans, which could be a useful tool in the precision management of inflammobesity [283]. Moreover, the expressions of genes with pro- and anti-inflammatory effects ultimately determine the outcome of inflammation [284]. Furthermore, metabolomics is an integrative approach that can be used to dissect the local and systemic metabolic consequences of inflammation, providing novel insights into the regulation of inflammatory diseases [285]. The application of these instruments are helping to elucidate unique and specific inflammo-metabotypes, expanding our understanding of the complexity and diversity of human metabolism [286]. Overall, these novel scientific insights are leading to the design and implementation of precision medicine/nutrition strategies for the prevention and control of prevalent chronic diseases with an inflammatory background [287].

Concluding Remarks

Nutrition is critical for life and well-being not only by contributing to disease prevention, health maintenance, and morbid conditions management, but also as a defense against endogenous and exogenous harmful factors including inflammation/oxidative stress or immune system dysfunctions. On the one hand, pro-inflammatory nutritional factors include the high consumption of foods rich in simple carbohydrates (fructose), SFA, TFA, cholesterol, and animal protein as well as habitually skipping breakfast and late overeating. On the other hand, potential anti-inflammatory compounds encompass MUFA, PUFA, antioxidant vitamins and minerals, bioactive molecules (polyphenols), specific foods (dairy products, whole-grains, fish, oilseeds, fruits and vegetables, edible insects, legumes, green tea, and coffee), culinary spices (cinnamon, ginger, back cumin, garlic, and turmeric) and some chrononutrition features including intermittent fasting and time-restricted eating (Fig. 1). Because inconsistencies and discrepancies between studies exist, further research in this field is still required, taking into account critical aspects of heterogeneity including type of population (ancestry), minimum and maximum levels and adverse effects, cooking methods, physiopathological status, and times of intervention. However, current evidence is contributing to the understanding of the relationship between nutrition and meta-inflammation, providing novel insights and potential targets for the control and management of communicable and non-communicable diseases.