1. Introduction
Inflammation has been regarded as a part of the body’s defense mechanisms against common pathogens or injuries. However, low-grade chronic inflammation, which is commonly associated with obesity and insulin resistance [
1,
2], termed meta-inflammation [
3], produces a steady subclinical inflammation throughout the body, ultimately resulting in major diseases such as cardiovascular disease, metabolic disorders and cancer [
4]. This type of inflammation is characterized by a sustained presence of peripheral inflammatory markers such as C-reactive protein (CRP) and various inflammatory cytokines such as nuclear factor kappa B (NF-κB), interleukin (IL)-6, tumor necrosis factor α (TNFα) and interferon-γ (INF-γ). Various endogenous and exogenous factors including aging, gender, exercise and diet are known to influence this type of inflammation [
5].
Fruits and vegetables as well as fiber, vitamin C, vitamin D and β-carotene have consistently shown to be associated with reducing chronic subclinical inflammation [
6]. However, the effect of diet on inflammation is more complicated because various pro- and anti-inflammatory components may interact and modify inflammation [
7]. The Western-style diet, which consists of high amounts of red meat, simple carbohydrates and refined grains, has been associated with higher levels of CRP and IL-6, whereas the Mediterranean diet, which consists of high amount of fresh fruits and vegetables, whole grains, nuts and fish along with high consumption of wine and olive oil, has been associated with lower levels of such pro-inflammatory markers [
8]. Because the traditional Korean diet (K-diet) is high in vegetables and fibers, moderate to high in legumes and fishes, and low in red meat and calories [
9], previous Korean nationwide studies have demonstrated the anti-oxidant and anti-inflammatory capability of K-diet with high phytochemical contents [
10,
11]. Even though a certain segment of Koreans still keep the traditional dietary pattern, the fast shift towards the Western style diet is occurring along with globalization in Korea [
12].
Although the cause and effect relationship is unclear and the degree and duration of inflammation that can contribute to the development of diseases remain to be elucidated [
4], emerging evidence indicates that maintaining an anti-inflammatory diet might be the most efficient strategy for reducing unhealthy inflammatory conditions [
6]. As low-grade inflammation progresses continuously and ultimately damages essential organs, the long-term provision of anti-inflammatory components through diet could be the most suitable physiologic modality as well as a relatively inexpensive and easy way to incorporate into lifestyle.
To determine the effect of diet on inflammation, a dietary inflammatory index (DII) has been developed [
8]. The original DII was developed to provide a tool that could categorize an individual’s diet into a spectrum from the highest to the lowest inflammatory diet. Thereafter, the DII has been further upgraded using literature that linked diet and inflammation as well as by incorporating cell culture, animal, and human studies [
11,
13]. The DII includes macro- and micro-nutrients as well as other bioactive food components such as flavonoids [
10]. Thus, the DII has been reported to be associated with a wide range of health conditions including metabolic disorders, cardiovascular diseases, cancer and neurocognitive diseases [
14].
Using a small dietary intervention study, we evaluated the anti-inflammatory properties of K-diet through the comparison of inflammatory biomarkers and DII with a current Westernized Korean diet [
15].
4. Discussion
Accumulating evidence strongly suggests that diet plays a fundamental role in the modulation of chronic subclinical inflammation. The K-diet rich in anti-inflammatory components has been regarded as a healthy diet [
10], which is expected to reduce chronic sustained inflammation.
In the present study, notably K-diet elevated the plasma IL-10 levels and lowered the NF-κB levels; further IL-10 levels were negatively correlated with the NF-κB levels in the K-diet group. IL-10, an immunoregulatory cytokine that has broad effects throughout the immune system, is the most important anti-inflammatory cytokine [
18]. NF-κB is an essential mediator of inflammatory response and its activation in macrophages initiates the inflammatory cascade [
19]. As IL-10 can block the activity of NF-κB, increased anti-inflammatory IL-10 due to K-diet consumption might down-regulate pro-inflammatory NF-κB.
Previous studies have demonstrated that IL-10 is an important protective cytokine against the chronic sustained inflammation commonly associated with aging, obesity, and diabetes mellitus. Evidence also suggests the cause and effect relationship between diet and IL-10. In an animal study, high-fat-diet-induced obesity significantly decreased IL-10 blood levels, while IL-10 treatment reduced inflammation induced by high-fat-diet [
20]. In an IL-10-deficient mouse model, age-associated endothelial dysfunction occurs earlier with IL-10 deficiency, and IL-10 protected the age-associated increase in the expression of IL-6, a pro-inflammatory cytokine [
21]. In a transgenic mouse model with muscle-specific IL-10 overexpression, IL-10 reduced insulin resistance and protected skeletal muscle from obesity-associated macrophage infiltration [
22]. In murine models of autoimmunity, IL-10 deficiency demonstrated disease exacerbation, while IL-10 overexpression illustrated immunosuppressive properties [
23]. Collectively, the elevation of IL-10 levels due to consumption of K-diet suggests that it may reduce inflammation and potentiate immunity.
NF-κB is a key regulator of energy metabolism and associated inflammation. Studies using mouse models of obesity have shown that high-fat diets can increase NF-κB activation, resulting in chronic prolonged inflammation and the elevation of other circulating pro-inflammatory cytokine levels [
24]. Recent evidence also indicates that the activation of NF-κB is critical for the development of insulin resistance [
25]. Clinical studies have demonstrated that high-fat meals can induce NF-κB activation from peripheral blood mononuclear cells and obese individuals have higher levels of NF-κB compared to lean individuals [
24]. Such studies have also provided evidence for a link between obesity and tumorigenesis conveyed through the NF-κB-dependent inflammatory response [
24]. Thus, reduced plasma levels of NF-κB in the K-diet group may indicate an anti-inflammatory effect of K-diet consumption and its subsequent positive effects on obesity, insulin resistance or tumorigenesis. In the K-diet group total cholesterol levels were decreased in parallel with the decrease in NF-κB levels due to lower consumption of cholesterol and animal fat, which is similar to that reported in a previous study [
26].
The average DII score of K-diet was −0.94 ± 1.39, which was lower than that of control group (1.04 ± 1.61). However, the DII score of control diet was still much lower than the reported score of maximally pro-inflammatory diet which is +7.98 [
13]. The DII scores of nutrients and foods in the K-diet were lower when compared to those of the control diet for 15 nutrients and 2 foods. However, the DII scores of the control diet were also lower when compared to those of K-diet for 7 nutrients and 2 foods, suggesting that control diet was not a high pro-inflammatory diet. If we had designed an increased pro-inflammatory diet, we might have obtained higher differences in pro-inflammatory mediators such as CRP, fibrinogen, IL-6, TNF-α, and IFN-γ levels compared to the control group. As our IRB strongly suggested not providing an unhealthy diet as a control, we used a modest pro-inflammatory control diet, which resulted in minimally high DII score for the control diet.
Compared with the control diet group, subjects in the K-diet group consumed more quantities of iron (
Table 4), which is known as a pro-inflammatory micronutrient [
27]; the DII score for iron was significantly higher in the K-diet group than in the control group (
Table 1). Nevertheless, hemoglobin levels decreased in the K-diet group but not in the control diet group. Although the K-diet group consumed more iron, its sources were plant based with low iron bioavailability (
Table 4). Furthermore, individuals in the K-diet group consumed much less red meat than in the control group (
Table 5). High iron consumption in the K-diet group increased the DII score but might not significantly contribute to inflammation due to low bioavailability of plant origin iron.
Carbohydrate DII score of the K-diet group was significantly higher than that of the control diet group (
Table 1), because carbohydrate consumption was higher in the K-diet group than in the control diet group (
Table 4). However, fasting blood glucose and insulin levels as well as HOMA-IR did not show significant changes in both groups, suggesting the effect of higher carbohydrate intake on inflammation might not be significant regardless of the higher DII score of carbohydrate. It is probably because the source of carbohydrate in the K-diet was mainly from the whole grains that have high dietary fiber content with low glycemic index and high anti-inflammatory properties [
28] (
Table 5).
Levels of TNF-α, IL6 and IFN-γ were not altered, which might be due to a limited subject number, a short duration, and modest pro-inflammatory properties of the control diet. TNF-α, a primary component of the obesity–diabetes mellitus link [
1], is a major pro-inflammatory cytokine involved in the early inflammatory phase and induces NF-κB production [
29]. Possibly, TNF-α levels did not change as IL-10 levels were elevated, which is a potent inhibitor of TNF-α [
30]. TNF-α blockade is also known to reduce insulin resistance and improve lipid profiles in individuals with chronic sustained inflammation [
31]. IL-6 also plays a central role in the pathogenesis of chronic diseases. The IL-6 signaling pathway mainly modulates the connection between aging and age-associated disorders [
32]. In the present study, IL-6 levels did not change, probably because NF-κB, which is the main modulator of IL-6, was downregulated. IFN-γ is a master checkpoint regulator of inflammatory cytokine process [
33] and orchestrates leukocyte attraction, natural killer (NK) cell activity and B cell functions [
34]. In fact, IFN-γ activates the pro-inflammatory NF-κB pathway [
35] and antagonized the anti-inflammatory IL-10 pathway [
36]. Thus, up-regulated IL-10 and down-regulated NF-κB might result in unchanged IFN-γ levels.
CRP and fibrinogen levels also did not change. CRP is an acute-phase reactant protein produced mainly in the liver in response to inflammatory stimulation [
37]. As CRP is influenced by diet, it has extensively been used as a major inflammatory biomarker that determines the dietary effects on inflammation. The association between CRP and diet mainly depends on the balance between pro-inflammatory and anti-inflammatory components of diet [
37]. In the present study, CRP levels did not change significantly, probably because the CRP levels of all subjects were within normal range from the beginning and both K-diet and control diet did not have high DII scores. Even though obesity is known to be associated with the elevation of CRP, our subjects whose BMIs were between 25 and 30 kg/m
2 (Asian obesity criteria is BMI 25 and higher) showed normal CRP levels. One positive finding was that CRP levels had a positive correlation with fasting blood insulin levels in both diet groups, which is similar to the previous report regarding the chronic systemic inflammation, BMI, insulin resistance and CRP [
38]. Fibrinogen, an independent risk factor for cardiovascular disease, is also a positive acute-phase reactant synthesized in the liver. Fibrinogen synthesis is triggered by the ingestion of a meal [
39]. Westernized diet increases [
40] and plant-based diet reduces serum fibrinogen levels [
41]. However, in the present study there was no significant change in the fibrinogen levels. Further study is necessary to determine the anti-inflammatory effects of K-diet on cardiovascular disease.
This study aimed to determine the anti-inflammatory features of K-diet by measuring the levels of blood inflammatory mediators and DII scores. Owing to the limited subject number and moderately pro-inflammatory control diet, significant results obtained were limited. However, levels of at least two major inflammatory cytokines showed significant differences along with significantly different DII scores. Future investigations with an increased number of subjects are warranted to clarify the anti-inflammatory effects of K-diet.