Exploring the differences in serum metabolite profiles after intake of red meat in women with rheumatoid arthritis and a matched control group.

PURPOSE: Studies have suggested that women with RA tend to avoid red meat more often than women without RA, based on their perception that it exacerbates their symptoms. Therefore, the aim of this study is to investigate and compare the postprandial metabolic response following the consumption of a red meat meal in patients with RA and a matched control group. METHODS: Participants were challenged with a meal with red meat and blood samples were collected before and at 0.5, 1, 2, 3 and 5 h after the meal. Serum metabolites were quantified by Nuclear Magnetic Resonance (NMR) analysis. Orthogonal Projections to Latent Structures with Discriminant Analysis (OPLS-DA) was used to evaluate separation by metabolites due to diagnosis of RA or not and to identify changes in metabolites related to RA. Incremental area under the curve was calculated for univariate comparisons for 23 metabolites. RESULTS: The matched groups, including 22 women with RA and 22 women without RA, did not differ significantly in age, body mass index, diet quality or reported physical activity. OPLS-DA models had a limited quality indicating that there were no differences in metabolite patterns between the groups. However, phenylalanine was significantly higher in concentration in women with RA compared to controls in both fasting and postprandial samples. CONCLUSION: To conclude, this well-controlled postprandial intervention study found a significantly higher concentration of phenylalanine in both fasting and postprandial samples of women with RA compared to matched women without RA. These findings warrant further investigation in larger studies. TRIAL REGISTRATION: The PIRA (Postprandial Inflammation in Rheumatoid Arthritis) trial is Registered at Clinicaltrials.gov (NCT04247009).

A randomized controlled cross-over trial investigating the acute inflammatory and metabolic response after meals based on red meat, fatty fish, or soy protein: the postprandial inflammation in rheumatoid arthritis (PIRA) trial.

PURPOSE: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. METHODS: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. RESULTS: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. CONCLUSION: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.

Towards objective measurements of habitual dietary intake patterns: comparing NMR metabolomics and food frequency questionnaire data in a population-based cohort.

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 1H 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.

Influence of Dietary n-3 Long Chain Polyunsaturated Fatty Acid Intake on Oxylipins in Erythrocytes of Women with Rheumatoid Arthritis.

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-É£-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.

Urine Metabolite Profiles and Nutrient Intake Based on 4-Day Weighed Food Diary in Habitual Vegans, Vegetarians, and Omnivores.

BACKGROUND: Increasing interest in diets excluding meat and other products of animal origin emphasizes the importance of objective and reliable methods to measure dietary exposure, to evaluate associations and causation between diet and health, and to quantify nutrient intakes in different diets. OBJECTIVES: This study aimed to investigate if NMR analysis of urine samples can serve as an objective method to discriminate vegan, vegetarian with or without fish, and omnivore diets. A secondary aim was to assess the influence of dietary nutrient intake on the metabolomics results. METHODS: Healthy individuals (43 men and 75 women, age 19-57 y) complying with habitual vegan (n = 42), vegetarian (n = 25), vegetarian + fish (n = 13), or omnivore (n = 38) diets were enrolled. Data were collected on clinical phenotype and lifestyle including a 4-d weighed food diary. Urine was analyzed for metabolites by NMR spectroscopy and data normalized using probabilistic quotient normalization and Pareto-scaled before multivariate analysis. Before orthogonal projections to latent structures with discriminant analysis, participants were assigned as meat consumers or nonmeat consumers (vegans and vegetarians), vegans or nonvegans (omnivores, vegetarian, and vegetarian + fish). RESULTS: The main results showed that it was possible to discriminate meat and nonmeat consumers (91% correctly classified), but discrimination between vegans and nonvegans was less rigorous (75% correctly classified). Secondary outcomes showed that reported intake of protein was higher in omnivores, and saturated fat lower and fiber higher in vegans, compared with the other groups. Discriminating metabolites were mainly related to differences in protein intake. CONCLUSIONS: NMR urine metabolomics appears suitable to objectively identify and predict habitual intake of meat in healthy individuals, but results should be interpreted with caution because not only food groups but also specific foods contribute to the patterns.This trial was registered at clinicaltrials.gov as NCT02039609.

Proposed Anti-Inflammatory Diet Reduces Inflammation in Compliant, Weight-Stable Patients with Rheumatoid Arthritis in a Randomized Controlled Crossover Trial.

BACKGROUND: It is unclear to what extent adjuvant dietary intervention can influence inflammation in rheumatoid arthritis (RA). OBJECTIVES: The objective was to assess the effects of dietary manipulation on inflammation in patients with RA. METHODS: In a crossover design, participants [n = 50, 78% females, median BMI (in kg/m2) 27, median age 63 y] were randomly assigned to begin with either a 10-wk portfolio diet of proposed anti-inflammatory foods (i.e., a high intake of fatty fish, whole grains, fruits, nuts, and berries) or a control diet resembling a Western diet with a 4-mo washout in between. This report evaluates the secondary outcome markers of inflammation among participants with stable medication. Analyses were performed using a linear mixed ANCOVA model. RESULTS: There were no significant effects on CRP or ESR in the group as a whole. In those with high compliance (n = 29), changes in ESR within the intervention diet period differed significantly compared with changes within the control diet period (mean: -5.490; 95% CI: -10.310, -0.669; P = 0.027). During the intervention diet period, there were lowered serum concentrations of C-X-C motif ligand 1 (CXCL1) (mean: -0.268; 95% CI: -0.452, -0.084;P = 0.006), CXCL5 (mean: -0.278; 95% CI: -0.530, -0.026 P = 0.031), CXCL6 (mean: -0.251; 95% CI: -0.433, -0.069; P = 0.009), and tumor necrosis factor ligand superfamily member 14 (TNFSF14) (mean: -0.139; 95% CI: -0.275, -0.002; P = 0.047) compared with changes within the control diet period. CONCLUSION: A proposed anti-inflammatory diet likely reduced systemic inflammation, as indicated by a decreased ESR in those who completed the study with high compliance (n = 29). These findings warrant further studies to validate our results, and to evaluate the clinical relevance of changes in CXCL1, CXCL5, CXCL6, and TNFSF14 in patients with RA.

Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA.

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 .

The 1H NMR serum metabolomics response to a two meal challenge: a cross-over dietary intervention study in healthy human volunteers.

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 1H 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, 1H 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.

A randomized controlled cross-over trial investigating the effect of anti-inflammatory diet on disease activity and quality of life in rheumatoid arthritis: the Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA) study protocol.

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 .

Orthorexia Nervosa Practices in Rheumatoid Arthritis: The DORA Study.

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.

Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment.

Autoimmune rheumatic diseases (AIRDs) constitute a set of connective tissue disorders and dysfunctions with akin clinical manifestations and autoantibody responses. AIRD treatment is based on a comprehensive approach, with the primary aim being achieving and attaining disease remission, through the control of inflammation. AIRD therapies have a low target specificity, and this usually propels metabolic disturbances, dyslipidemias and increased cardiovascular risk. Ceramides are implicated in inflammation through several different pathways, many of which sometimes intersect. They serve as signaling molecules for apoptosis, altering immune response and driving endothelial dysfunction and as regulators in the production of other molecules, including sphingosine 1-phosphate (S1P) and ceramide 1-phosphate (C1P). With lipid metabolism being severely altered in AIRD pathology, several studies show that the concentration and variety of ceramides in human tissues is altered in patients with rheumatic diseases compared to controls. As a result, many in vitro and some in vivo (animal) studies research the potential use of ceramides as therapeutic targets in rheumatoid arthritis (RA), ankylosing spondylitis, systemic lupus erythematosus, fibromyalgia syndrome, primary Sjögren's syndrome, systemic sclerosis, myositis, systemic vasculitis and psoriatic arthritis. Furthermore, the majority of ceramide synthesis is diet-centric and, as a result, dietary interventions may alter ceramide concentrations in the blood and affect health. Subsequently, more recently several clinical trials evaluated the possibility of distinct dietary patterns and nutrients to act as anti-ceramide regimes in humans. With nutrition being an important component of AIRD-related complications, the present review details the evidence regarding ceramide levels in patients with AIRDs, the results of anti-ceramide treatments and discusses the possibility of using medical nutritional therapy as a complementary anti-ceramide treatment in rheumatic disease.

Mind the Gap: Tools for the Diagnosis and Assessment of Orthorexia Nervosa Based on the Recent Consensus Definition. Reply to Meule, A. Comment on "Sifakaki et al. Orthorexia Nervosa Practices in Rheumatoid Arthritis: The DORA Study. Nutrients 2023, 15, 713".

In a recent manuscript, our team published the results of an original pilot cross-sectional study assessing orthorexia nervosa (ON) tendencies among patients with rheumatoid arthritis (RA) [...].

Inadequate Dietary Nutrient Intake in Patients With Rheumatoid Arthritis in Southwestern Sweden: A Cross-Sectional Study.

Background: Patients with rheumatoid arthritis (RA), who suffer from impaired physical function and fatigue, may have difficulties with grocery shopping and preparing meals. Also, to improve symptoms, patients often experiment with diets but seldom consult a dietitian. Although this could lead to a nutritiously deprived diet, an up-to-date, thorough description of the nutrient intake in Swedish patients with RA is absent. Here, we investigated the habitual dietary energy and nutrient intake in patients with RA living in southwestern Sweden. Materials and Methods: Three-day food records performed at two time points during the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial, were used. The intake of energy and nutrients was analyzed using The Swedish Food Composition Database. Results: A total of 62 participants (50 females, 12 males) were included in the study, where 18 participants completed one 3-day food record and 44 participants completed two 3-day food records. Median (IQR) intake of total fat was above or in the upper range of recommendations (females: 37.1 [32.5, 41.7] energy percent (E%), and males: 40.3 [37.5, 42.9] E%). Median (IQR) intake of saturated fatty acids exceeded recommendations (females: 14.9 [12.5, 17.0] E% and males: 15.4 [12.2, 17.0] E%), while median (IQR) carbohydrate and fiber intakes were below recommendations (females: 41.7 [36.3, 45.4] E% and 17.2 [12.8, 20.9] g, respectively, and males: 38.8 [35.2, 40,3] E% and 18.5 [15.7, 21.0] g, respectively). The reported intake of other macronutrients was in line with recommendations. For several micronutrients, e.g., vitamin A and D, folate, and calcium, median intake was below recommended intake. Vitamin A intake was especially low and did not reach lower intake level (LI) for 14 and 17% of females and males, respectively. For females, about 10% did not reach LI for vitamin D, calcium, and riboflavin. Conclusion: We found that patients with RA residing in southwestern Sweden reported a high intake of saturated fatty acids and low intake of fiber and several micronutrients. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1], identifier [NCT02941055].

Validity of bioimpedance for assessment of fat-free mass in women with Rheumatoid Arthritis compared to non-rheumatic controls.

BACKGROUND & AIMS: The aim was to assess the validity of bioimpedance in the assessment of fat free mass (FFM) among women and to study if the validity differs between women with and without Rheumatoid Arthritis (RA). METHODS: 38 women with RA and 24 non-rheumatic controls were included. FFM was measured in the non-fasting state using DXA (Lunar Prodigy), multi-frequency bioelectrical impedance analysis (BIA) (MF-BIA [Tanita MC-180 MA]), single-frequency BIA (SF-BIA) and bioelectrical impedance spectroscopy (BIS) (both Impedimed SFB7). BIS raw data were also used to calculate FFM from equations by Matthie, Jaffrin and Moissl. Results were compared using correlation, Bland Altman analysis, Mann Whitney U test and Wilcoxon Signed Ranks Test. RESULTS: Women with RA had different body water distribution compared to women without RA (p < 0.05). Median bias in FFM assessed by bioimpedance was 0.62-7.87 kg with wide limits of agreement for all methods. Median FFM differed significantly from DXA by all bioimpedance methods except for BIS by Jaffrin. Women with RA had significantly smaller biases compared to non-rheumatic controls using BIS equations by Matthie (p = 0.012) and Moissl (p = 0.025). Correlations between FFM measured by DXA and bioimpedance (r = 0.73-0.85, all p < 0.001) did not differ between groups. The sensitivity of bioimpedance to detect low fat free mass index (FFMI) was 0-47%. CONCLUSION: The results of this study show that bioimpedance has similar validity in women with RA compared to non-rheumatic controls, despite differences in body water distribution. Agreement with DXA improved when applying specific equations, but the clinical utility of bioimpedance is questionable as all methods failed to identify low FFMI with acceptable precision. TRIAL REGISTER: Clinicaltrials.org, NCT04247009.

Improvements in Body Composition after a Proposed Anti-Inflammatory Diet Are Modified by Employment Status in Weight-Stable Patients with Rheumatoid Arthritis, a Randomized Controlled Crossover Trial.

Rheumatoid Arthritis (RA) is an autoimmune disease affecting peripheral joints. Chronic activation of inflammatory pathways results in decreased function and the development of comorbidities, such as loss of lean mass while retaining total body mass. The objective of this report was to assess whether dietary manipulation affects body composition in patients with RA as a secondary outcome. Fifty patients were included in a randomized controlled crossover trial testing a proposed anti-inflammatory Mediterranean-style diet compared to a Western diet. Body composition was measured by bioelectrical impedance spectroscopy in patients without implants (n = 45). Regardless of treatment, fat-free mass increased and fat mass percentage decreased during weight stability, but no differences between intervention and control in the whole group (n = 42, all p > 0.20) were found. Interaction analysis revealed that participants who were non-employed (n = 15) significantly decreased in fat mass (−1.767 kg; 95% CI: −3.060, −0.475, p = 0.012) and fat mass percentage (−1.805%; 95% CI: −3.024, −0.586, p = 0.008) from the intervention compared to the control period. A Mediterranean-style diet improved body composition in non-employed participants (n = 15). The group as a whole improved regardless of dietary allocation, indicating a potential to treat rheumatoid cachexia by dietary manipulation.

Identification of Single and Combined Serum Metabolites Associated with Food Intake.

Assessment of dietary intake is challenging. Traditional methods suffer from both random and systematic errors; thus objective measures are important complements in monitoring dietary exposure. The study presented here aims to identify serum metabolites associated with reported food intake and to explore whether combinations of metabolites may improve predictive models. Fasting blood samples and a 4-day weighed food diary were collected from healthy Swedish subjects (n = 119) self-defined as having habitual vegan, vegetarian, vegetarian + fish, or omnivore diets. Serum was analyzed for metabolites by 1H-nuclear magnetic resonance spectroscopy. Associations between single and combined metabolites and 39 foods and food groups were explored. Area under the curve (AUC) was calculated for prediction models. In total, 24 foods or food groups associated with serum metabolites using the criteria of rho > 0.2, p < 0.01 and AUC ≥ 0.7 were identified. For the consumption of soybeans, citrus fruits and marmalade, nuts and almonds, green tea, red meat, poultry, total fish and shellfish, dairy, fermented dairy, cheese, eggs, and beer the final models included two or more metabolites. Our results indicate that a combination of metabolites improve the possibilities to use metabolites to identify several foods included in the current diet. Combined metabolite models should be confirmed in dose−response intervention studies.

Changes in serum and urinary metabolomic profile after a dietary intervention in patients with irritable bowel syndrome.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: Participants were randomized to a low fermentable oligo-, di-, monosaccharide and polyol (FODMAP) diet (LFD) or traditional IBS diet (TID) for four weeks. Fasting serum and urine samples pre- and post-intervention were analyzed using 1H nuclear magnetic resonance (NMR) metabolomics. Response to treatment was defined as a reduction in IBS severity scoring system (IBS-SSS) ≥50. RESULTS: 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. CONCLUSIONS: 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. CLINICAL TRIAL REGISTRATION: This trial was registered at www.clinicaltrials.gov, registry number NCT02107625.

A Randomized Controlled Dietary Intervention Improved the Serum Lipid Signature towards a Less Atherogenic Profile in Patients with Rheumatoid Arthritis.

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.

Effects on health-related quality of life in the randomized, controlled crossover trial ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis).

BACKGROUND: Patients with Rheumatoid Arthritis (RA) often report impaired health-related quality of life (HrQoL) such as difficulties in daily life, pain, fatigue and an affected social life. Even when lowering disease activity, pharmacological treatment does not always resolve these factors. OBJECTIVE: To investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA. DESIGN: 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. RESULTS: Forty-seven participants completed ≥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). CONCLUSIONS: 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.

Do Interventions with Diet or Dietary Supplements Reduce the Disease Activity Score in Rheumatoid Arthritis? A Systematic Review of Randomized Controlled Trials.

The aim was to compile the evidence from Randomized Controlled Trials (RCTs) of diet or dietary supplements used to reduce disease activity in adults with Rheumatoid Arthritis (RA). Searches were performed in the databases PubMed, Scopus and Cochrane. Only RCT studies of diets, foods or dietary supplements, looking at effects on the Disease Activity Score in 28 joints (DAS28) among adults with RA, published in peer-reviewed journals, were included. A total of 27 articles were included-three of whole diets (Mediterranean diet, raw food and anti-inflammatory diet), five of food items, five of n-3 fatty acids, five of single micronutrient supplements, four of single antioxidant supplements and five of pre-, pro- or synbiotics. Studies that showed moderate strength evidence for positive effects on disease activity in RA included interventions with a Mediterranean diet, spices (ginger powder, cinnamon powder, saffron), antioxidants (quercetin and ubiquinone), and probiotics containing Lactobacillus Casei. Other diets or supplements had either no effects or low to very low strength of evidence. In conclusion, RCT studies on diet or dietary supplements are limited in patients with RA, but based on the results in this review there is evidence that some interventions might have positive effects on DAS28.