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.

Nutritional intake and determinants of nutritional quality changes from pregnancy to postpartum-a longitudinal study.

Nutrient requirements vary across the reproductive cycle, but research on changes in nutritional intake and quality from pregnancy to beyond the lactation period is limited. Thus, we aimed to study nutritional intake and quality changes, among Swedish pregnant participants from late pregnancy to 18 months postpartum and to study the determinants of nutritional quality changes. Participants (n = 72) were studied longitudinally from the third trimester of pregnancy and postpartum (2 weeks 4, 12, and 18 months postpartum). At each visit, participant characteristics and 4-day food diaries were collected. Nutritional quality was assessed by energy adjusted Nutrient Rich Food Index 11.3. Linear mixed models were used to analyze the determinants of change in nutritional quality. Intakes of carbohydrate energy percentage (E%), fiber, vitamin A, vitamin C, and potassium were higher in the third trimester compared to postpartum, whereas intakes of E% protein and monounsaturated fat were lower. Adherence to recommended intakes was low at all study visits for saturated fat (4%-11%), fiber (15%-39%), vitamin D (8%-14%), folate (0%-2%), and iron (6%-21%). Overall, nutritional quality did not differ significantly from third trimester to postpartum. Shorter duration (<4 months) of lactation was negatively related to nutritional quality changes, whereas higher age was positively related to changes. In conclusion, nutritional intake from pregnancy to postpartum changed, whereas quality remained relatively stable, with age and lactation duration as determinants. Identification of people at risk of adverse dietary changes from pregnancy to the postpartum period should be further addressed in future larger and more diverse study populations.

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).

Patients with radiographic axial spondylarthritis have an impaired dietary intake-a cross-sectional study with matched controls from northern Sweden.

BACKGROUND: Radiographic axial spondyloarthritis (r-axSpA) is one of the most common chronic inflammatory rheumatic diseases, affecting about 0.2% of the Swedish population. Adequate nutritional intake is essential for maintaining physiological functions. A poor diet increases the risk of developing conditions such as obesity, osteoporosis, and/or atherosclerosis. Diet quality is also theorized to affect systemic inflammation. Dietary habits in patients with r-axSpA are largely unknown. The aims of this study were to assess dietary nutrient intake in r-axSpA patients and examine whether it differs compared to persons without r-axSpA. METHODS: r-axSpA patients (modified NY criteria) at the rheumatology clinic in Region Västerbotten, northern Sweden, were invited to take part in the Backbone study which investigates disease severity and comorbidities. In total, 155 patients were included. Nutritional intake was assessed by the semi-quantitative food frequency questionnaire MiniMeal-Q. Controls were collected from the Swedish CArdioPulmonary bioImage Study (n = 30,154), a study that invited participants 50-64 years of age by random selection from the Swedish population register. Out of the 155 r-axSpA patients, 81 were in the same age span. Four controls were identified for each patient, matched on age (± 1 year), sex, and geographic location. Data on dietary intake was available for 319 controls. Statistical comparisons of dietary intake between patients with r-axSpA and controls were done by exact conditional logistic regression analysis, adjusted for country of birth, educational level, single household, weight, smoking status, and energy intake. RESULTS: Patients had a comparatively significantly higher energy intake from carbohydrates, a lower fiber density, and a lower intake of marine omega-3 fatty acids. Furthermore, intake of vitamins D, E, and K as well as selenium, folate, calcium, magnesium, phosphorus, potassium, vitamin A, and ß-carotene (a precursor of vitamin A and marker of vegetable and fruit intake) was significantly lower among patients compared to controls. CONCLUSIONS: Our results suggest that r-axSpA patients have an impaired dietary intake. Notably, intake was lower in several nutrients theorized to have anti-inflammatory properties (fiber density, marine-omega-3 fatty acids, vitamin D, and selenium). We further propose that nutrition screening might be incorporated into the management of r-axSpA patients.

Dietary biomarkers and food records indicate compliance to study diets in the ADIRA (Anti-inflammatory Diet In Rheumatoid Arthritis) trial.

Background: In the ADIRA (Anti-inflammatory Diet In Rheumatoid arthritis) trial, compliance to the study diets has previously been described primarily with a score based on reported intake of trial foods from telephone interviews. The aim of this study was to evaluate compliance using objective dietary biomarkers for whole grain, fruit and vegetables, margarine and oil, seafood and overall fat quality, as well as reported intake from food records of key components of the study diets. Methods: Fifty patients with rheumatoid arthritis were randomized to begin with the intervention diet (rich in whole grain, fruit and vegetables, margarine/oil and seafood) or the control diet (rich in meat and high-fat dairy) for 10 weeks, followed by a ~ 4 months wash-out period, and then switched diet. Compliance was evaluated using plasma alkylresorcinols (AR) as biomarkers for intake of whole grain wheat and rye, serum carotenoids for fruit and vegetables, plasma linoleic acid (LA, 18:2 n-6) and -α-linolenic acid (18:3, n-3) for margarine and cooking oil, plasma eicosapentaenoic acid (EPA, 20:5 n-3), -docosahexaenoic acid (DHA 22:6, n-3) and -docosapentaenoic acid (22:5 n-3) for seafood, and plasma fatty acid pattern for the overall dietary fat quality. Reported intake of whole grain, fruit, berries and vegetables, seafood, red meat, and fat quality was extracted from 3-d food records. Results: Plasma AR C21:0 and C23:0, LA, EPA, and DHA were higher while total serum carotenoids were lower after the intervention diet period compared to the control diet period (AR and carotenoids: p = <0.05, fatty acids: p = <0.001). Reported intake of whole grain, fruit, berries and vegetables, and seafood was higher and reported intake of red meat was lower during the intervention diet period compared to the control diet period (p = <0.001). Plasma- and reported fatty acid pattern differed as intended between the diet periods. Conclusion: This study indicates that the participants in the ADIRA trial were compliant to the study diets regarding intake of whole grain, cooking fat, seafood, and red meat, and the intended overall dietary fat quality. Compliance to instructions on fruit- and vegetable intake remains uncertain. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02941055?term=NCT02941055&draw=2&rank=1, NCT02941055.

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].

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.

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.

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.

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 .

Anti-inflammatory Diet In Rheumatoid Arthritis (ADIRA)-a randomized, controlled crossover trial indicating effects on disease activity.

BACKGROUND: Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking. OBJECTIVES: We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA. METHODS: In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR). Secondary outcomes were changes in the components of DAS28-ESR (tender and swollen joints, ESR, and visual analog scale for general health) and DAS28-C-reactive protein. RESULTS: In the main analysis, a linear mixed ANCOVA model including the 47 participants completing ≥1 diet period, there was no significant difference in DAS28-ESR between the intervention and control periods (P = 0.116). However, in unadjusted analyses, DAS28-ESR significantly decreased during the intervention period and was significantly lower after the intervention than after the control period in the participants who completed both periods (n = 44; median: 3.05; IQR: 2.41, 3.79 compared with median: 3.27; IQR: 2.69, 4.28; P = 0.04, Wilcoxon's Signed Rank test). No significant differences in the components were observed. CONCLUSIONS: This trial indicates positive effects of a proposed anti-inflammatory diet on disease activity in patients with RA. Additional studies are required to determine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055.

Tomato-based randomized controlled trial in prostate cancer patients: Effect on PSA.

BACKGROUND & AIMS: The effect of lycopene-containing foods in prostate cancer development remains undetermined. We tested whether a lycopene-rich tomato intervention could reduce the levels of prostate specific antigen (PSA) in prostate cancer patients. METHODS: Prior to their curative treatment, 79 patients with prostate cancer were randomized to a nutritional intervention with either 1) tomato products containing 30 mg lycopene per day; 2) tomato products plus selenium, omega-3 fatty acids, soy isoflavones, grape/pomegranate juice, and green/black tea (tomato-plus); or 3) control diet for 3 weeks. RESULTS: The main analysis, which included patients in all risk categories, did not reveal differences in changes of PSA-values between the intervention and control groups. Post-hoc, exploratory analyses within intermediate risk (n = 41) patients based on tumor classification and Gleason score post-surgery, revealed that median PSA decreased significantly in the tomato group as compared to controls (-2.9% and +6.5% respectively, p = 0.016). In separate post-hoc analyses, we observed that median PSA-values decreased by 1% in patients with the highest increases in plasma lycopene, selenium and C20:5 n-3 fatty acid, compared to an 8.5% increase in the patients with the lowest increase in lycopene, selenium and C20:5 n-3 fatty acid (p = 0.003). Also, PSA decreased in patients with the highest increase in lycopene alone (p = 0.009). CONCLUSIONS: Three week nutritional interventions with tomato-products alone or in combination with selenium and n-3 fatty acids lower PSA in patients with non-metastatic prostate cancer. Our observation suggests that the effect may depend on both aggressiveness of the disease and the blood levels of lycopene, selenium and omega-3 fatty acids.