A high intake of fruits and vegetables has been inversely associated with metabolic syndrome features [5, 6], cardiovascular diseases [31, 32], and total mortality , while greater values of proinflammatory markers such acute-phase proteins, cytokines, and adhesion molecules have been directly associated with chronic disorders [2, 3]. In this context, the potential relationships between specific dietary factors and proinflammatory markers are being currently investigated [19–21, 34]. In this context, nutrigenomic approaches have been performed as a potential useful tool to increase fundamental knowledge concerning the interactions between diet and gene expression [13, 14]. Thus, this study found, apparently for first time, that healthy adults with a high consumption of fruits and vegetables had lower ICAM1, IL1R1, IL6, TNFα, and NFκB1(p50) gene expression in PBMC.
An altered expression of ILs, TNFα, ICAM1 genes and of their respective receptors in adipose tissue as well as in PBMC has been implicated in the higher risk of suffering metabolic syndrome and cardiovascular disease [3, 4, 35]. In addition, NFκB is a redox-sensitive transcription factor implicated in the transmission of different signals from the cytoplasm to the nucleus, which are involved in the regulation of inflammatory and immune genes, apoptosis, and cell proliferation . In this regard, the activation of this transcription factor has been involved in atherosclerosis . Therefore, the reported inverse association between fruits and vegetable consumption and the selected proinflammatory gene expression measurements suggest a new clinically relevant mechanism concerning the prevention of subclinical inflammation status in healthy adults by a high intake of fruits and vegetables.
In this study, we also found a statistically significant inverse association of fruit and vegetable consumption with CRP and homocysteine concentrations. These results are consistent with some earlier cross-sectional studies carried out on children and adolescents [38, 39] as well as middle-age adults [7, 40]. Moreover, in a randomized crossover study, the addition of vegetables to the diet has been able to reverse the increase in circulating vascular adhesion molecule-1 (VCAM1), ICAM1, IL6, and TNFα levels, as induced by a single high-fat (saturated) meal consumption . Furthermore, in a randomized controlled 4-week trial, a high consumption (eight vs. two servings/day) of fruits and vegetables also significantly reduced CRP levels .
The anti-inflammatory mechanisms related to fruit and vegetable consumption are still unclear. Fruits and vegetables are sources of essential nutrients, which could be implicated in inflammation and oxidative stress reductions [10, 41]. For example, the intake of folate, vitamin C, and magnesium, for those fruits and vegetables have relevant content, have been associated with lower homocysteine, CRP, IL6 and E-selectin concentrations [42–44]. Fruits and vegetables also are important sources of dietary fiber, which appears to have an anti-inflammatory role [10, 41]. Also, dietary fiber intake could participate in weight control and favor weight loss, hypoglycemic actions and hypolipidemic effects . In addition, butyrate production after the consumption of dietary fiber could have an inhibitory effect on the NFκB and a stimulatory effect on PPAR-α activation, with subsequent lower expression of ICAM1 and VCAM1 genes , although this mechanism deserves further research. Furthermore, fruits and vegetables contain several flavonoids and carotenoids with recognized antioxidant properties, which may play a role in the inverse relationship between intake of fruits and vegetables and inflammatory status [9, 38, 47]. In fact, several in vitro studies have evidenced an anti-inflammatory effect of flavonoids and carotenoids, by an inhibition of NFκB activity, through suppressing the activation-related phosphorylation, and inhibiting the nuclear translocation [48–50].
In this study, we also found inverse associations of dietary fiber and TAC with plasma concentrations and the gene expression of certain proinflammatory markers, suggesting a participation of these specific dietary factors in the beneficial effect of fruit and vegetable consumption. The gene expression of investigated proinflammatory markers had statistically significant lower values across tertiles of fruit and vegetable consumption, independently of dietary fiber and dietary TAC. In addition, the inverse associations of fruit and vegetable consumption with proinflammatory gene expression maintained the trend and the statistical significance after including others specific dietary factors such as plant protein, potassium, magnesium, total fat, polyunsaturated fatty acid and saturated fatty acid. In this context, our findings suggest that additive and synergistic effects of bioactive compounds provided by fruits and vegetables as responsible for the antioxidant and anti-inflammatory activities of these foods.
Interestingly, we found lower values to BMI, waist circumference, and blood pressure in those participants who were in the highest tertile of fruit and vegetable consumption. These results are in accordance with findings obtained in the SUN Study [5, 51] and in The Dietary Approaches to Stop Hypertension (DASH) trial [52, 53]. In turn, it has been also reported a positive association of proinflammatory marker concentrations and gene expression in PBMC with body fat distribution  in healthy young adults. Thus, the relationships between fruit/vegetable consumption and proinflammatory markers could be biased by body fat composition. When we controlled our analyses by these potential confounding factors, including BMI or waist circumference as continuous independent variables, the hypothesized associations between fruit and vegetable consumption and proinflammatory markers maintained the trend and the statistical significance, suggesting that the effects of fruit and vegetable consumption that we found in this study were not totally explained by differences in body fat variables. Our study had certain limitations. First, since the nature of this study is cross-sectional, we cannot prove that the reported associations are causal because residual confounding may have affected the observed associations. However, we controlled for the more important known factors that affect proinflammatory gene expression. Second, dietary exposures can be misclassified despite the good correlation between food frequency questionnaires and usual diet  but the dietary questionnaire is validated , and has been successfully applied to investigate the relationship between dietary factors and inflammatory markers [19–21]. Third, a higher consumption of oranges and tomatoes as well as the contribution of the remaining food items to the fruit and vegetable consumption could be influenced by the season in which the questionnaires were completed , although the SUN food-frequency questionnaire has presented a good reproducibility  in different circumstances. Fourth, although the sample size is adequate from the standpoint of initial association discovery, further replication in independent and larger samples will be convenient for a future translational application at a population level.