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Oxylipins derived from n-3 fatty acids are suggested as the link between these fatty acids and reduced inflammation. The aim of the present study was to explore the effect of a randomized controlled cross-over intervention on oxylipin patterns in erythrocytes. Twenty-three women with rheumatoid arthritis completed 2 × 11-weeks exchanging one cooked meal per day, 5 days a week, for a meal including 75 g blue mussels (source for n-3 fatty acids) or 75 g meat. Erythrocyte oxylipins were quantified by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The results were analyzed with multivariate data analysis. Orthogonal projections to latent structures (OPLS) with effect projections and with discriminant analysis were performed to compare the two diets’ effects on oxylipins. Wilcoxon signed rank test was used to test pre and post values for each dietary period as well as post blue-mussel vs. post meat. The blue-mussel diet led to significant changes in a few oxylipins from the precursor fatty acids arachidonic acid and dihomo-ɣ-linolenic acid. Despite significant changes in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and free EPA in erythrocytes in the mussel group, no concurrent changes in their oxylipins were seen. Further research is needed to study the link between n-3 fatty-acid intake, blood oxylipins, and inflammation.

Background Low-quality, non-diverse diet is a main risk factor for premature death. Accurate measurement of habitual diet is challenging and there is a need for validated objective methods. Blood metabolite patterns reflect direct or enzymatically diet-induced metabolites. Here, we aimed to evaluate associations between blood metabolite patterns and a priori and data-driven food intake patterns. Methods 1, 895 participants in the Northern Sweden Health and Disease Study, a population-based prospective cohort study, were included. Fasting plasma samples were analyzed with 1 H Nuclear Magnetic Resonance. Food intake data from a 64-item validated food frequency questionnaire were summarized into a priori Healthy Diet Score (HDS), relative Mediterranean Diet Score (rMDS) and a set of plant-based diet indices (PDI) as well as data driven clusters from latent class analyses (LCA). Orthogonal projections to latent structures (OPLS) were used to explore clustering patterns of metabolites and their relation to reported dietary intake patterns. Results Age, sex, body mass index, education and year of study participation had significant influence on OPLS metabolite models. OPLS models for healthful PDI and LCA-clusters were not significant, whereas for HDS, rMDS, PDI and unhealthful PDI significant models were obtained (CV-ANOVA p  < 0.001). Still, model statistics were weak and the ability of the models to correctly classify participants into highest and lowest quartiles of rMDS, PDI and unhealthful PDI was poor (50%/78%, 42%/75% and 59%/70%, respectively). Conclusion Associations between blood metabolite patterns and a priori as well as data-driven food intake patterns were poor. NMR metabolomics may not be sufficiently sensitive to small metabolites that distinguish between complex dietary intake patterns, like lipids.

To investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA. In this controlled crossover trial, 50 patients were randomized to start with either an intervention diet (anti-inflammatory) or a control diet (usual Swedish intake) for ten weeks followed by a wash out period before switching to the other diet. Participants received food equivalent to ~1100 kcal/day, five days/week, and instructions to consume similarly for the remaining meals. HrQoL was evaluated using Health Assessment Questionnaire (HAQ), 36-item Short Form Survey (SF-36), Visual Analogue Scales (VAS) for pain, fatigue and morning stiffness, and a time scale for morning stiffness. Forty-seven participants completed [greater than or equal to]1 diet period and were included in the main analyses. No significant difference between intervention and control diet at end of diet periods was observed for any outcome. However, significant improvements were obtained for SF-36 Physical Functioning (mean:5.79, SE: 2.12, 95% CI: 1.58, 10.01) during the intervention diet period. When excluding participants with anti-rheumatic medication changes, the differences between diet periods increased for most outcomes, favoring the intervention diet period, and the difference for SF-36 Physical Functioning became significant (n = 25, mean:7.90, 95% CI:0.56, 15.24, p = 0.036). In main analyses, the proposed anti-inflammatory diet did not significantly improve HrQoL for patients with RA compared to control diet. In sub-analyses, significant improvements in physical functioning were detected. Larger studies with consistent medication use and in populations more affected by the disease may be needed to obtain conclusive evidence.

Irritable bowel syndrome (IBS) is a multi-faceted gastrointestinal disorder where food intake often triggers symptoms. Metabolomics may provide mechanistical insights to why responses to dietary modifications are diverse. This study aimed to identify metabolite patterns related to dietary intake in patients with IBS, and to identify metabolites driving the separation between responders and non-responders to treatment. Twenty-five individuals in the LFD (13 responders) and 28 in the TID (14 responders) were included in these post hoc analyses. In endpoint samples, significant decreases in polyols and glucose were seen in the LFD. Post-intervention samples revealed that LFD responders had significantly increased levels of 2-hydroxybuturate and decreased levels of glucose and pantothenic acid compared to non-responders. For the TID, only weak multivariate models were identified and a larger diversity in metabolite response compared to the LFD were noted. In this study, metabolite patterns between individuals who responded well to an LFD compared to non-responders could be distinguished. This provides new hypotheses for mechanistic actions related to response to dietary modifications, but the results need to be validated in larger cohorts.

Background The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA. Methods Patients ( n  = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure. Results Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention ( p  = 0.007 and p  = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention ( p  = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period. Conclusion Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA. Trial registration This trial is registered at ClinicalTrials.gov as NCT02941055 .

Background Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5–1.0% of the population, and where many patients in spite of modern pharmacological treatment fail to reach remission. This affects physical as well as mental wellbeing and leads to severely reduced quality of life and reduced work capacity, thus yielding high individual as well as societal costs. As a complement to modern pharmacological treatment, lifestyle intervention should be evaluated as a treatment option. Scientific evidence exists for anti-inflammatory effects by single foods on RA, but no study exists where these foods have been combined to obtain maximum effect and thus offer a substantial improvement in patient life quality. The main goal of the randomized cross-over trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) is to test the hypothesis that an anti-inflammatory diet intervention, compared to a regular diet, will decrease disease activity and improve quality of life in patients with stable established RA. Methods In total, 50 RA patients with moderate disease activity are randomized to receive initially either a portfolio diet based on several food items with suggested anti-inflammatory effects or a control diet during 2 × 10 weeks with 3 months wash-out between diets. Food bags are delivered weekly by a home food delivery chain and referred to as the fiber bag and the protein bag, respectively, to partially blind participants. Both groups continue with regular pharmacological treatment. Known food biomarkers will be analyzed to measure intervention compliance. Impact on disease severity (measured by DAS28, a composite score which predicts disability and progression of RA), risk markers for cardiovascular disease and quality of life are evaluated after each diet regimen. Metabolomics will be used to evaluate the potential to predict responders to dietary treatment. A health economic evaluation is also included. Discussion The nutritional status of patients with RA often is poor and many ask their physician for diet advice. No evidence-based dietary guidelines for patients with RA exist because of the paucity of well-conducted sufficiently large diet intervention trials. ADIRA is an efficacy study and will provide evidence as to whether dietary treatment of RA can reduce disease activity and improve quality of life as well as reduce individual and societal costs. Trial registration ClinicalTrials.gov Registration Number: NCT02941055 .

Medical nutrition therapy (MNT) is an indisputable component of the multidisciplinary therapeutic approach in rheumatoid arthritis (RA). Previous research has suggested that in chronic disease where nutrition is an important effector of prognosis, healthy dietary choices might take an unhealthy turn, with patients developing disordered eating in the form of orthorexia nervosa (ON). ON is characterized by a pathological preoccupation with “healthy”, “pure” eating, associated with restrictive dietary patterns, nutrient deficiencies and worsening disease outcomes. The aim of the present cross-sectional study was to evaluate ON tendencies in a sample of adult patients with RA. A total of 133 patients with RA were recruited, and completed the ORTO-15 questionnaire for the assessment of ON tendencies. Most of the patients were overweight/obese (53.4%). The results revealed ON tendencies in the sample, with the median ORTO-15 score reaching 36 (IQR: 33–39). Greater ON tendencies were associated with the female gender, and lowered ON tendencies with increasing age and body mass index. The present findings highlight the need for health professional awareness regarding the problem of ON in patients with RA and the importance of screening patients.

Background The risk of atherosclerotic cardiovascular disease (ASCVD) is increased in Rheumatoid Arthritis (RA). Previous research has suggested that lipid metabolism is altered in RA, but research under postprandial conditions is scarce. The aim of this study was to investigate whether women with RA have a different lipemic and inflammatory response to a mixed meal containing red meat compared to women without RA. Methods Twenty-two women with RA, with modest disease activity, and 22 women without RA matched for age and body mass index (BMI) at the group level consumed a hamburger meal containing ca. 700 kcal (53 E% from fat, 27 E% from carbohydrate). Venous blood was sampled in the fasted state and after 30 min, 1, 2, 3 and 5 h and analysed for lipid species using nuclear magnetic resonance spectroscopy. Postprandial inflammation was measured by interleukin- 6 (IL- 6). The postprandial lipid response was calculated as the incremental area under the curve minimal value, and serial measurements were analysed by repeated measures analysis of variance. Lipid and inflammatory responses were compared by linear regression analysis, adjusted for age, BMI, physical activity, and baseline plasma concentration. Results Plasma concentrations of IL- 6, triglycerides (TGs) and very low-density lipoprotein (VLDL) particles increased significantly after the meal compared to baseline within both groups, but no differences were observed between groups. However, the women with RA had a less pronounced response in cholesterol carried in VLDL particles ( p  = 0.03) and in TGs in the subfraction of VLDL particles with highest density ( p  = 0.03). No association was found between the response in TGs and IL- 6. Conclusion This study does not provide compelling evidence for any difference in the lipemic or inflammatory response in women with RA compared with age- and BMI-matched women without RA following ingestion of a mixed, high-fat meal containing red meat. The modest disease activity in women with RA should be considered when interpreting these findings. Subtle group differences found in the lipids carried by VLDL particles warrant further investigation. Trial registration The PIRA (Postprandial Inflammation in Rheumatoid Arthritis) trial was registered 2020–01 - 28 at Clinicaltrials.gov (NCT04247009).

Background Metabolomics represents a powerful tool for exploring modulation of the human metabolome in response to food intake. However, the choice of multivariate statistical approach is not always evident, especially for complex experimental designs with repeated measurements per individual. Here we have investigated the serum metabolic responses to two breakfast meals: an egg and ham based breakfast and a cereal based breakfast using three different multivariate approaches based on the Projections to Latent Structures framework. Methods In a cross over design, 24 healthy volunteers ate the egg and ham breakfast and cereal breakfast on four occasions each. Postprandial serum samples were subjected to metabolite profiling using 1 H nuclear magnetic resonance spectroscopy and metabolites were identified using 2D nuclear magnetic resonance spectroscopy. Metabolic profiles were analyzed using Orthogonal Projections to Latent Structures with Discriminant Analysis and Effect Projections and ANOVA-decomposed Projections to Latent Structures. Results The Orthogonal Projections to Latent Structures with Discriminant Analysis model correctly classified 92 and 90% of the samples from the cereal breakfast and egg and ham breakfast, respectively, but confounded dietary effects with inter-personal variability. Orthogonal Projections to Latent Structures with Effect Projections removed inter-personal variability and performed perfect classification between breakfasts, however at the expense of comparing means of respective breakfasts instead of all samples. ANOVA-decomposed Projections to Latent Structures managed to remove inter-personal variability and predicted 99% of all individual samples correctly. Proline, tyrosine, and N-acetylated amino acids were found in higher concentration after consumption of the cereal breakfast while creatine, methanol, and isoleucine were found in higher concentration after the egg and ham breakfast. Conclusions Our results demonstrate that the choice of statistical method will influence the results and adequate methods need to be employed to manage sample dependency and repeated measurements in cross-over studies. In addition, 1 H nuclear magnetic resonance serum metabolomics could reproducibly characterize postprandial metabolic profiles and identify discriminatory metabolites largely reflecting dietary composition. Trial registration Registered with ClinicalTrials.gov, identifier: NCT02039596 . Date of registration: January 17, 2014.

Diet is a major modifiable risk factor for cardiovascular disease (CVD). One explanation for this is its effect on specific lipids. However, knowledge on how the lipidome is affected is limited. We aimed to investigate if diet can change the new ceramide- and phospholipid-based CVD risk score CERT2 and the serum lipidome towards a more favorable CVD signature. In a crossover trial (ADIRA), 50 patients with rheumatoid arthritis (RA) had 10 weeks of a Mediterranean-style diet intervention or a Western-style control diet and then switched diets after a 4-month wash-out-period. Five hundred and thirty-eight individual lipids were measured in serum by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Lipid risk scores were analyzed by Wilcoxon signed-rank test or mixed model and lipidomic data with multivariate statistical methods. In the main analysis, including the 46 participants completing ≥1 diet period, there was no significant difference in CERT2 after the intervention compared with the control, although several CERT2 components were changed within periods. In addition, triacylglycerols, cholesteryl esters, phosphatidylcholines, alkylphosphatidylcholines and alkenylphosphatidylcholines had a healthier composition after the intervention compared to after the control diet. This trial indicates that certain dietary changes can improve the serum lipid signature towards a less atherogenic profile in patients with RA.