Per Magne Ueland

Aims: Carnitine-metabolites play a key role in cell energy metabolism and have been implicated in the pathogenesis of atrial fibrillation (AF). However, any associations between L-carnitine and the precursor γ-butyrobetaine (γBB) with new-onset AF are not established. We therefore examined the relationship between serum γBB, L-carnitine and selected acylcarnitines with incident AF. Methods and results: We studied 3815 patients who underwent coronary angiography due to suspected chronic coronary syndrome and followed up for incident CVD events, including new-onset AF. Risk associations between the biomarkers and incident AF were explored by logistic regression for the total population and stratified according to sex. The majority (71.6%) of the patients were men, the median age was 61 years. Over a median follow-up of 7.3 years, 412 (10.8%) were reported with new-onset AF. In a multivariate model higher serum γBB, L-carnitine and palmitoylcarnitine [OR per 1SD (95% CI): 1.15 (1.01–1.31), P = 0.04; 1.14 (1.01–1.27), P = 0.03 and 1.15 (1.03–1.28), P = 0.01] were associated with increased risk of incident AF. These associations were particularly stronger among women (P for interaction < 0.04, all). Conclusion: In this large cohort of patients with suspected chronic coronary syndrome elevated circulating levels of γBB, L-carnitine and palmitoylcarnitine were associated with increased risk of incident AF, with stronger associations among women. Our results motivate further studies examining the relationship between carnitine metabolites and cardiac arrhythmias and highlight the need for sex specific analyses.

Aim: Indoles are tryptophan (Trp)‐derived metabolites that are produced by the gut microbiota and may influence the gut‐microbiota‐brain axis in multiple sclerosis (MS). Indole‐3‐lactate (ILA) is reduced in persons with MS and improves MS clinical scores in animal models via its anti‐inflammatory remyelinating properties. The ILA/indole‐3‐acetate (IAA) (ILA/AA) index is considered a neuroprotection index. Physical exercise and diet can modify gut microbiota and indole metabolism. Methods: This secondary analysis of a randomized control trial aimed to assess the effects of acute and chronic exercise on serum indoles in relapsing–remitting MS (RRMS). Thirty‐one RRMS patients (≥ 70% session attendance) completed a 10 week multimodal functional training (60 min, 3×/week) vs. a waitlist control group. Blood samples were collected at baseline and compared to a matched healthy control group, and after 10 weeks for the assessment of chronic effects. Additionally, acute effects of a single bout of exercise were assessed with a blood sample before, during, and immediately after one interim training session. Serum indole concentrations were measured using LC–MS/MS. Results: Baseline indole levels in RRMS patients differed from those of matched healthy controls, and reduced ILA levels were observed. The 10 week intervention increased the ILA/IAA index, while a single exercise bout induced an increase in both ILA and ILA/IAA. Conclusion: Multimodal functional training over 10 weeks led to an improved ILA/IAA index suggesting a neuroprotective shift in gut microbiota composition, and a single bout acutely increases the circulating level of ILA. Study registration number: DRKS00017091.

Background: Exclusive breastfeeding for the first 6 months of corrected age (CA) is recommended for premature infants with very low birth weight (n = 35) and at 2 (n = 47), 6 (n = 48), and 12 months (n = 58) CA. Results: Only a minority of the infants were given multivitamin supplementation, and this was associated with higher PLP and riboflavin levels. One-third of the infants were exclusively breastfed to 6 months CA, and these had lower cobalamin, PLP, and riboflavin concentrations compared to formula-fed infants; additionally, 80% had plasma tHcy concentrations ≥ 6.5 µmol/L, indicative of cobalamin deficiency during the first 6 months CA. Serious deficiency of one or more B vitamins was evident in 3–9% of the infants at each time point during the first 12 months CA, more often in breastfed infants, but not exclusively. Conclusions: Exclusive breastfeeding with inadequate multivitamin supplementation and no specific recommendation for introduction of solid food does not provide an adequate B vitamin status in infants born prematurely with VLBW. Nutritional micronutrient recommendations must be improved, and regular evaluation of vitamin status should be implemented in the follow-up for premature VLBW infants.

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Table from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Supplementary Table from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment

Background:Fatigue is often reported by colorectal cancer survivors and largely impacts their quality of life. Inflammation has been linked to fatigue mainly in patients with breast cancer. Therefore, we investigated how inflammation is longitudinally associated with fatigue in colorectal cancer survivors, up to 2 years posttreatment.Methods:A total of 257 patients from the ongoing Energy for life after ColoRectal cancer cohort study were included in the analysis. Plasma levels of IL6, IL8, IL10, TNFα, high-sensitivity C-reactive protein (hsCRP), and fatigue were measured at 6 weeks, 6, 12, and 24 months posttreatment. Fatigue was measured through the validated Checklist Individual Strength (CIS; total, 20–140), consisting of four subscales – subjective fatigue (8–56), motivation (4–28), physical activity (3–21), and concentration (5–35), and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 fatigue subscale (0–100). Linear mixed-models were used to assess the confounder-adjusted longitudinal associations between inflammatory markers and overall fatigue along with the subscales.Results:Mean levels of CIS fatigue decreased from 62.9 at 6 weeks to 53.0 at 24 months. In general, levels of inflammatory markers also decreased over time. No statistically significant longitudinal associations were found between IL6, IL8, IL10, TNFα, and fatigue. Higher levels of hsCRP were associated with more CIS fatigue (β per SD 3.21, 95% confidence interval (CI), 1.42–5.01) and EORTC fatigue (β 2.41, 95% CI, 0.72–4.10).Conclusions:Increased levels of hsCRP are longitudinally associated with more posttreatment fatigue in colorectal cancer survivors.Impact:These findings suggest that low-grade inflammation may play a role in fatigue reported by colorectal cancer survivors up to 2 years posttreatment.

Supplementary Figure from Longitudinal Associations between Inflammatory Markers and Fatigue up to Two Years after Colorectal Cancer Treatment