Obesity has become a major health problem worldwide, and it is strongly associated with a series of diseases such as insulin resistance, type 2 diabetes, asthma, arterial hypertension, atherosclerosis, certain forms of neoplasia, and ischemic heart disease, which reduce life expectancy and, together, have enormous economic and social consequences.^1,2

Metabolic syndrome has been recognized as a complication of obesity, and it is associated with increased risk of diabetes, hypertension, and dyslipidemias. Insulin resistance, chronic inflammation, and increased oxidative stress play an essential role in the development of pathogenesis.^3,4 Nevertheless, there is a group of individuals who, in spite of the risks, do not develop metabolic syndrome.⁴ This phenotype is called metabolically healthy obese. These individuals have a lower amount of visceral fat, smaller adipocytes, and lower levels of inflammation when compared to metabolically unhealthy obese individuals.⁴

Oxidative stress is referred to as excessive production of reactive oxygen species that the antioxidant system cannot neutralize.⁵ Inflammation, on the other hand, is the response to threats received by the organism, which can be the entry of pathogens, chronic and autoimmune diseases, tobacco use, alcohol consumption, hypercaloric diet, and others.⁵ Many of these conditions favor the production of reactive oxygen species, resulting in oxidative stress and increased signaling of inflammatory molecules.⁵

Among the factors related to lifestyle, diet has a relevant influence, although there is no consensus regarding the role of diet in metabolic phenotypes.⁶ Current evidence suggests that metabolically healthy individuals have similar intake of calories and macronutrients compared to metabolically unhealthy obese individuals.⁶ Furthermore, diet is a strong moderator of chronic systemic inflammation; for instance, “unhealthy” dietary patterns (Western-style diets with high fat, refined carbohydrate, and protein content) are typically associated with higher concentrations of inflammatory markers, whereas “healthier” diets (for example, the Mediterranean diet high in fruits, vegetables, and fish) are associated with lower levels of inflammation.⁷

The Dietary Inflammatory Index (DII) was developed by researchers at the University of South Carolina to estimate overall dietary inflammatory potential based on extensive literature research that incorporates cell culture, animal, and epidemiological studies on the effects of diet on inflammation.⁸ The DII has been shown to be associated with inflammation, specifically in concentrations of C-reactive protein, interleukin (IL)-6, and tumor necrosis factor alpha in adults.⁹ The association between dietary inflammatory potential and metabolic syndrome continues to be highly controversial. In two systematic reviews, the results were contradictory.^10,11

Thus, the objective of this study was to investigate dietary inflammatory potential between metabolic phenotypes and to compare the biochemical, anthropometric, clinical, and socioeconomic differences, as well as differences between anti-inflammatory and pro-inflammatory diets in individuals with the same metabolic phenotype.

We evaluated 533 volunteers, 237 in the MHPI, 44 in the MHAI group, 202 in the MUPI group, and 50 in the MUAI group. In the supplementary material we display the characteristics of the study groups. The groups with metabolically unhealthy phenotype presented higher frequency of illiteracy, higher per capita income and higher frequency of cardiovascular diseases, diabetes, systemic arterial hypertension, dyslipidemia and higher cardiovascular risk in relation to metabolically healthy phenotypes. Regarding energy intake, we did not observe a significant difference between the groups studied, however, a higher consumption of antioxidant vitamins (A, C and E) and flavonoids was verified in the MHAI and MUAI groups, respectively.

The mean DII of the total sample was 0.974±1.02, with a maximum of 4.34 and a minimum of −1.74. By separating the groups according to the metabolic phenotype and inflammatory characteristic of the diet, we observed a significant difference between the groups with the same metabolic phenotype (MHAI versus MHPI and MUPI versus MUAI; p<0.05) and between the MHAI versus MUPI and MHPI versus MUAI groups (Table 1).

When comparing the groups of the same metabolic phenotype, we found that there was no statistical difference in relation to anthropometric, biochemical, and blood pressure measurements between the metabolically healthy groups with the pro-inflammatory and anti-inflammatory diets. In the metabolically unhealthy groups, we found a statistical difference in relation to systolic and diastolic blood pressure. When comparing the 4 groups, we observed a difference between the anthropometric (BMI, WC and NC) and biochemical (Glycemia, HDL and triglycerides) parameters between the groups with unhealthy metabolic phenotype in relation to the healthy metabolic phenotype and pro-inflammatory diet. The group with healthy metabolic phenotype and anti-inflammatory diet also had significantly lower concentrations of glucose and triglycerides and higher concentrations of HDL cholesterol compared to the 2 groups with unhealthy metabolic phenotype (Table 1).

When evaluating the serum concentrations of isoprostanes, we found that the metabolically healthy and anti-inflammatory group had significantly lower values when compared to the metabolically healthy and pro-inflammatory (p = 0.023), however, we did not observe statistical difference when comparing the four study groups, as displayed in Table 2.

In regression analysis (Table 2), the only variable that demonstrated a higher risk of alterations in all groups when compared to the metabolically healthy and anti-inflammatory group were isoprostane concentrations. When comparing the unhealthy groups, we found that participants with a pro-inflammatory diet had a greater likelihood of having higher systolic blood pressure values.

This study evaluated the association of the metabolic phenotypes of obesity with dietary inflammatory potential. We demonstrated that metabolically healthy individuals on an anti-inflammatory diet had lower concentrations of isoprostanes. Furthermore, when compared to the metabolically healthy and the anti-inflammatory groups, the other groups showed a higher risk of showing changes in this marker. In addition, individuals with unhealthy metabolic phenotype and pro-inflammatory diet were more likely to have higher systolic blood pressure values.

As expected, the groups with unhealthy metabolic phenotypes had higher abdominal adiposity, blood glucose, blood pressure, and lipid profile alterations when compared to groups with healthy metabolic phenotypes. These results are consistent with previous studies that showed differences in these individuals’ anthropometric and biochemical characteristics.^23,24 Some factors have been suggested to explain the profile of metabolically healthy obesity. For instance, the smaller size of adipocytes, lower ectopic fat accumulation, and greater intestinal integrity are associated with reduced systemic inflammation, and greater insulin sensitivity.²⁵

Dietary pattern has also been associated with the development of obesity phenotypes. In 2019, Kouvari et al. evaluated data from the ATTICA study in 1514 men and 1528 women over 18 years of age in Athens, Greece and observed that 52% of participants developed an unhealthy metabolic state during the 10-year follow-up, and metabolically healthy obesity was independently associated with increased risk of cardiovascular disease in participants with low adherence to the Mediterranean diet. Subsequently, the same researchers showed an inverse association between DII and transition from a healthy to unhealthy metabolic state and diabetes, concluding that a diet with a high anti-inflammatory load appears to be an effective preventive measure to maintain a metabolically healthy state.^26,27

Systematic reviews evaluating the relationship between DII and metabolic syndrome have reported a high degree of heterogeneity.^10,11 These results may be due to the difference in the study populations, with different habits, lifestyles, and cultures.

Few studies in the literature have associated DII with phenotype of obesity, which makes comparisons difficult. A study carried out in Iran with 300 obese individuals, mostly female, with a mean age of 43 years, mostly classified as metabolically unhealthy (63.5%) according to the criteria used in our study, showed that the mean DII of this sample was −0.33 ± 1.60,²⁸ and they observed an increased likelihood for the unhealthy metabolic phenotype as the diet became more pro-inflammatory.²⁸ In general, our sample showed a DII with more pro-inflammatory characteristics, but, when comparing individuals with the same metabolic phenotype according to dietary inflammatory potential, we did not observe differences in the metabolic characteristics of these individuals. Park et al., investigating the association of DII scores, metabolic phenotypes, and mortality risk in overweight/obese individuals from a representative sample of the United States, showed that a more pro-inflammatory diet is associated with an increased risk of all-cause mortality and cardiovascular mortality, only in the metabolically unhealthy obese phenotype,²⁹ which leads us to question whether this association is influenced by a less healthy lifestyle and not only by the dietary inflammatory characteristic.

In order to expand knowledge on this topic, we divided the volunteers into 4 groups according to metabolic phenotype and dietary inflammatory. To our knowledge, this is the first study in Brazil to evaluate this association. When evaluating dietary inflammatory potential, we observed a variation of −1.74 to +4.34, different from other studies carried out in Brazil, which found variations of −4.77 to +5.98,³⁰ −5.48 to +4.55,³¹ and −4.69 and +5.28.³² This can be explained by the fact that our population was composed of individuals with obesity, while others were from a general population. According to the results of the study by Pereira et al.,³⁰ the Brazilian population consumes a diet with high inflammatory potential, especially adolescents who are overweight and obese, white people, and people with higher income and education. The fact that these researchers included adolescents in their study may justify the higher DII values when compared to our results. According to the authors, this may be due to the fact that adults and elderly individuals with chronic diseases tend to improve the quality of their diet as they become more concerned about health.³⁰ Other studies carried out in young adults in Brazil found that pro-inflammatory dietary patterns were associated with a higher prevalence of overweight and obesity in both men and women,³¹ whereas the study conducted by Carvalho et al., with adults 23 to 25 years of age in Ribeirão Preto, Brazil, did not find the association of the DII with insulin resistance and metabolic syndrome, probably because these individuals were young and the effects of a pro-inflammatory diet on the development of these outcomes had not yet manifested.³²

When comparing the unhealthy phenotype groups, we found a significant difference in relation to blood pressure and, when moving to regression analysis, we continued to observe this difference in systolic blood pressure, which leads us to suggest that dietary inflammatory capacity may influence the increase in blood pressure among unhealthy individuals. In fact, a 2018 systematic review concluded that the prevalence of hypertension and systolic blood pressure measurements are higher in more pro-inflammatory dietary categories, which was not seen in diastolic blood pressure.³³ However, other studies have found a weak association between DII and the prevalence of hypertension in adult women,³⁴ as well as a weak association between DII and blood pressure in a sample of adolescents.³⁵

Finally, we verified whether the concentrations of isoprostanes, a marker of oxidative stress, were different between groups according to the metabolic phenotype and according to the inflammatory capacity of the diet. Isoprostane has been considered a good marker of oxidative stress, given that it is specific for lipid peroxidation, chemically stable, found in detectable amounts in tissues and biological fluids, and not affected by the lipid content of the diet. Elevated concentrations of this marker were found in patients with several cardiovascular risk factors such as diabetes, obesity, hypercholesterolemia, and smoking.³⁶ An article published analyzing the Framingham study volunteers reached the conclusion that obesity is associated with a state of excessive oxidative stress, which may contribute to the prevalence of cardiovascular disease in this population.³⁷ When evaluating the association between obesity phenotypes and oxidative stress markers, Lejawa et al., found that total oxidation state and total antioxidant capacity (TAC), as well as concentrations of lipid hydroperoxides were significantly related to metabolically unhealthy obesity.³⁸ Jakubiak et al., evaluated young individuals, between 18 and 36 years of ages, without any history of chronic diseases, also observing that metabolically unhealthy obese patients had higher oxidative stress parameters compared to patients with normal weight and no metabolic disorders.³⁹

Our results showed that individuals with healthy metabolic phenotypes and who consumed an anti-inflammatory diet had lower concentrations of isoprostanes, which leads us to suppose that the anti-inflammatory diet may possibly protect obese individuals from exacerbation of oxidative stress.³⁹ We did not find in the literature studies that made this assessment in individuals with different metabolic phenotypes of obesity, which limits us to make comparisons. However, we verified two studies that compared DII with oxidative stress. Zhang et. al observed a significant and positive correlation between the Children's Dietary Inflammatory Index (C-DII) with indicators of oxidative stress (serum bilirubin, albumin and iron) when evaluating children and adolescents, and this association was more pronounced in those who were overweight and obese.⁴⁰ Moradi et al., evaluated the relationship between DII and serum markers of oxidative stress in a case-control study with 121 patients with non-alcoholic fatty liver disease (NAFLD) and 119 healthy individuals and observed a correlation between DII with malondialdehyde (MDA) and total antioxidant capacity only in the group of healthy individuals.⁴¹ Despite the few studies on the association of IDD with oxidative stress, it has been shown that healthy dietary patterns are composed of foods that are sources of bioactive compounds, such as antioxidants, polyphenols, micronutrients, and polyunsaturated fatty acids; in this manner, they can attenuate inflammation, reduce oxidative stress, and reduce the risk of metabolic syndrome.⁴²

This study has some limitations. As it is an observational study, causality cannot be inferred. Because the dietary characteristics of this sample were more pro-inflammatory, the number of individuals in the anti-inflammatory diet groups was much smaller, which may have influenced the results. That notwithstanding, this study has some strengths, including the facts that it is the only study in Brazil to evaluate obese individuals according to their phenotype and the first to evaluate dietary characteristics according to each metabolic phenotype, in addition to evaluation of oxidative stress.

We are able to conclude that an anti-inflammatory diet is associated with lower oxidative stress in metabolically healthy obese, and a pro-inflammatory diet is associated with higher systolic blood pressure value.