Objective: To perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator.Design: Using data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (≤3 mg/l, >3 mg/l), while controlling for important potential confounders.Setting: Existing data from the Seasonal Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational study of healthy participants recruited in Worcester, MA, USA and participants were followed for 1 year.Subjects: Participants who had at least one hs-CRP measurement over her/his 1-year participation (n495 for 24HR,n559 for 7DDR).Results: Higher DII scores were associated with values of hs-CRP >3 mg/l (OR = 1·08; 95 % CI 1·01, 1·16,P= 0·035 for the 24HR; and OR = 1·10; 95 % CI 1·02, 1·19,P= 0·015 for the 7DDR).Conclusions: The population-based DII was associated with interval changes in hs-CRP using both the 24HR and 7DDR. The success of this first-of-a-kind attempt at relating individuals’ intakes of inflammation-modulating foods using this refined DII, and the finding that there is virtually no drop-off in predictive capability using a structured questionnaire in comparison to the 24HR standard, sets the stage for use of the DII in a wide variety of other epidemiological and clinical studies.

Background: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven

Many dietary factors have either proinflammatory or anti-inflammatory properties. We previously developed a dietary inflammatory index (DII) to assess the inflammatory potential of diet. In this study, we conducted a construct validation of the DII based on data from a food frequency questionnaire and three inflammatory biomarkers in a subsample of 2567 postmenopausal women in the Women's Health Initiative Observational Study. We used multiple linear and logistic regression models, controlling for potential confounders, to test whether baseline DII predicted concentrations of interleukin-6, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha receptor 2, or an overall biomarker score combining all three inflammatory biomarkers. The DII was associated with the four biomarkers with beta estimates (95% confidence interval) comparing the highest with lowest DII quintiles as follows: interleukin-6: 1.26 (1.15-1.38), Ptrend < .0001; tumor necrosis factor alpha receptor 2: 81.43 (19.15-143.71), Ptrend = .004; dichotomized hs-CRP (odds ratio for higher vs. lower hs-CRP): 1.30 (0.97-1.67), Ptrend = .34; and the combined inflammatory biomarker score: 0.26 (0.12-0.40), Ptrend = .0001. The DII was significantly associated with inflammatory biomarkers. Construct validity of the DII indicates its utility for assessing the inflammatory potential of diet and for expanding its use to include associations with common chronic diseases in future studies.

To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk. Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses’ Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatography-tandem mass spectrometry. We observed substantial metabolomic variation with respect to Mediterranean diet adherence, with nearly one-third of the assayed metabolites significantly associated with MEDAS (false discovery rate < 0.05). Using elastic net regularized regressions, we identified a metabolic signature, comprised of 67 metabolites, robustly correlated with Mediterranean diet adherence in both PREDIMED and NHS/HPFS (r = 0.28–0.37 between the signature and MEDAS; P = 3 × 10⁻³⁵ to 4 × 10⁻¹¹⁸). In multivariable Cox regressions, the metabolic signature showed a significant inverse association with CVD incidence after adjusting for known risk factors (PREDIMED: hazard ratio [HR] per standard deviation increment in the signature = 0.71, P < 0.001; NHS/HPFS: HR = 0.85, P = 0.001), and the association persisted after further adjustment for MEDAS scores (PREDIMED: HR = 0.73, P = 0.004; NHS/HPFS: HR = 0.85, P = 0.004). Further genome-wide association analysis revealed that the metabolic signature was significantly associated with genetic loci involved in fatty acids and amino acids metabolism. Mendelian randomization analyses showed that the genetically inferred metabolic signature was significantly associated with risk of coronary heart disease (CHD) and stroke (odds ratios per SD increment in the genetically inferred metabolic signature = 0.92 for CHD and 0.91 for stroke; P < 0.001). We identified a metabolic signature that robustly reflects adherence and metabolic response to a Mediterranean diet, and predicts future CVD risk independent of traditional risk factors, in Spanish and US cohorts.

Colorectal cancer is the third most commonly diagnosed cancer in both men and women in the United States.¹ Inflammation plays an important role in cancer development, including colorectal cancer.^2,3 Though epidemiological studies have not consistently reported significant associations between prediagnosis levels of widely used inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF), and colorectal cancer risk,⁴ there is plausible evidence that inflammation plays an important role in colorectal cancer development. For example, obesity, a state of low-grade chronic inflammation,⁵ has been associated with colorectal cancer risk.⁶ Chronic inflammation may also contribute to insulin resistance and hyperinsulinemia, which are associated with colon cancer risk. Also, chronic inflammation has been implicated as a key predisposing factor to colorectal cancer in inflammatory bowel disease.⁷ Furthermore, several studies have shown that the use of anti-inflammatory medications, such as aspirin, can reduce colorectal cancer development.⁸ Intervention studies have shown that diet modulates inflammation^9,10; therefore, dietary patterns with higher inflammatory potential may influence colorectal cancer risk.