Study protocol: fish oil supplement in prevention of oxaliplatin-induced peripheral neuropathy in adjuvant colorectal cancer patients - a randomized controlled trial. (OxaNeuro).

BACKGROUND: Oxaliplatin-induced peripheral neuropathy (OIPN) in general and painful OIPN in particular is a debilitating late effect that severely affects cancer survivors' quality of life and causes premature cessation of potentially lifesaving treatment. No preventive treatments and no effective treatment for chronic OIPN exist despite many attempts. One of several suggested mechanisms includes neuroinflammation as a contributing factor to OIPN. Fish oil containing long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFAs) are precursors to specialized proresolving mediators that mediate the resolution of inflammation. Our primary hypothesis is that a high supplementation of n-3 LCPUFAs will lower the prevalence and severity of OIPN. METHODS: The OxaNeuro project is an investigator-initiated, multicenter, double-blinded, randomized, placebo-controlled clinical study. We will include 120 patients eligible to receive adjuvant oxaliplatin after colorectal cancer surgery. Patients will receive fish oil capsules containing n-3 LCPUFAs or corn oil daily for 8 months. The primary endpoint is the prevalence of OIPN at 8 months defined as relevant symptoms, including one of the following: abnormal nerve conduction screening, abnormal vibration threshold test, abnormal skin biopsy, or abnormal pinprick test. Additional endpoints include the intensity and severity of OIPN-related neuropathic pain, patient-reported OIPN symptoms, quality of life, mental health symptoms, body composition, and cognitive evaluation. Furthermore, we will evaluate inflammatory biomarkers in blood samples and skin biopsies, including the potential OIPN biomarker neurofilament light protein (NfL) which will be measured before each cycle of chemotherapy. DISCUSSION: If readily available fish oil supplementation alleviates OIPN prevalence and severity, it will significantly improve the lives of both cancer survivors and palliative cancer patients receiving oxaliplatin; it will improve their quality of life, optimize chemotherapeutic treatment plans by lowering the need for dose reduction or premature cessation, and potentially increase survival. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT05404230 Protocol version: 1.2, April 25th. 2023.

The effect of traditional diet on glucose homoeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: a randomised crossover study.

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type 2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised crossover study consisting of two 4-week dietary interventions: Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western diet, the Traditional diet reduced mean and maximum daily blood glucose by 0·17 mmol/l (95 % CI 0·05, 0·29; P = 0·006) and 0·26 mmol/l (95 % CI 0·06, 0·46; P = 0·010), respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0·5 kg (95 % CI; 0·09, 0·90; P = 0·016) relative to the Western diet and 4 % (95 % CI 1, 9; P = 0·018) lower LDL:HDL-cholesterol, which after adjustment for weight loss appeared to be driven by HDL elevation (0·09 mmol/l (0·03, 0·15), P = 0·006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p = 0·093), which reflected a non-significant increase of 1·4 (-0·6, 3·5) mmol/l in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

Fish oil supplementation may improve attention, working memory and attention-deficit/hyperactivity disorder symptoms in adults with autism spectrum disorder: a randomised crossover trial.

Marine n-3 fatty acids (n-3LCPUFA) have shown neurocognitive benefits in children with attention-deficit/hyperactivity disorder (ADHD), but few trials have examined effects in adults with autism spectrum disorder (ASD). We explored, if n-3LCPUFA affect cognitive functions in adults with ASD, and if effects are modified by comorbid ADHD. In a 2 × 4 week crossover study, twenty-six participants were randomised to sequence of supplementation with fish oil (FO, 5·2 g/d n-3PUFA) and safflower oil (SO). At baseline and after each period, we measured primary outcomes: attention (d2-test) and spatial working memory (Corsi test) and secondary outcomes: flexibility (Stroop word-colour test), ADHD symptoms (Conners scales), executive functions (Behavioural Inventory of Executive Function) and social behaviour (Social Responsiveness Scale). The dropout rate was 15 %. Compliance was 94 % and correlated with whole-blood n-3LCPUFA. Corsi scores improved by ∼0·3 × sd (P = 0·032) after FO v. SO, and the odds for d2 errors were 30 % lower (P = 0·016), which was supported by improved Conners scores of attention (P = 0·023). Improvement in Conners ADHD symptom score was limited to participants with ADHD (-3·5(-6·0; -1·0), n 10 v. -0·2(-2·5;2·2), n 11 without ADHD, Pinteraction = 0·096), who also improved their behavioural regulation index by 0·3 × sd after FO (Pinteraction = 0·016). Participants without ADHD gained most in d2 test performance (OR = 0·4(0·2;0·7) v. 0·9(0·6;1·3) in those with ADHD, Pinteraction = 0·002), but their executive function score was exacerbated after FO (5·9(0·0,11·8), Pinteraction = 0·039). Our results did not show any effects on ASD symptoms, but suggest that FO may improve attention and working memory in adults with ASD and ameliorate ADHD symptoms in those with comorbid ADHD.

Wholegrain intake, growth and metabolic markers in Danish infants and toddlers: a longitudinal study.

PURPOSE: Wholegrain intake is linked to lower risk of lifestyle diseases, but little is known about its role in growth and metabolic health during the first years of life. We characterized wholegrain and dietary fibre intake in 439 Danish children at 9 and 36 months of age and explored associations with height z-scores (HAZ), body mass index z-scores (BMIZ) and metabolic markers. METHODS: We used pooled data from two infant cohorts and estimated intakes of total wholegrain, dietary fibre and wholegrain subtypes from 7-day dietary records. Associations with HAZ, BMIZ and non-fasting plasma low-density (LDLC) and high-density-lipoprotein cholesterol, triacylglycerol, insulin and glucose were analysed in mixed models, adjusted for potential confounders. RESULTS: Median (25th, 75th percentile) wholegrain intake was 7.5 (4.9, 10.5) and 6.5 (4.6, 9.0) g/MJ at 9 and 36 months. Neither wholegrain nor dietary fibre intake were associated with HAZ (P ≥ 0.09). At 36 months, wholegrain intake was inversely associated with LDLC (P = 0.05) and directly with glucose (P < 0.001). In secondary analyses, wholegrain rye was inversely associated with glucose at 9 months and insulin at 36 months (both P ≤ 0.03). Oat and wheat wholegrain were directly associated with glucose (both P ≤ 0.01) and wheat with BMIZ (P = 0.02) at 36 months. CONCLUSION: Danish infants and toddlers have high intakes of wholegrain and dietary fibre, with no indication of compromised growth. In line with studies in adults, wholegrain intake was inversely associated with LDLC. The observed direct association between wholegrain intake and plasma glucose and associations with wholegrain subtypes should be investigated further.

Effect of Fish Oil Supplementation on Hyperlipidemia during Childhood Acute Lymphoblastic Leukemia Treatment - A Pilot Study.

Hyperlipidemia is common during contemporary treatment of childhood acute lymphoblastic leukemia and may increase risk of osteonecrosis, thrombosis, and possibly acute pancreatitis. Marine fatty acids found in fish oil decrease levels of triglycerides and possibly total cholesterol in hyperlipidemic patients. This prospective pilot study provided fish oil for 83 days to seven children undergoing acute lymphoblastic leukemia treatment. On average fish oil was consumed 74% of the intervention period. Further, we found significant lower levels of triglycerides (P = 0.016) and total cholesterol (P = 0.027) compared to 22 historical controls, although correction for one extra PEG-asparaginase dose reduced the level of significance. However, the findings indicate that fish oil may alleviate development of hyperlipidemia during acute lymphoblastic leukemia treatment. Randomized controlled trials are warranted to confirm these findings and to investigate the potential effect of fish oil supplements on development of severe adverse events, including osteonecrosis, thrombosis, and acute pancreatitis.

Does polymorphisms in PPAR and APOE genes modify associations between fatty acid desaturase (FADS), n-3 long-chain PUFA and cardiometabolic markers in 8-11-year-old Danish children?

n-3 Long-chain PUFA (LCPUFA) can improve cardiometabolic blood markers, but studies in children are limited. SNP in the FADS genes, which encode fatty acid desaturases, influence endogenous LCPUFA production. Moreover, SNP in genes that encode PPAR and apoE may modulate the effects of n-3 LCPUFA. We explored whether FADS polymorphisms were associated with blood cholesterol and TAG, insulin and glucose and whether polymorphisms in PPAR and APOE modified associations between FADS or n-3 LCPUFA status and the cardiometabolic blood markers. We measured fasting cholesterol and TAG, insulin, glucose and n-3 LCPUFA in 757 Danish 8-11-year-old children and genotyped SNP in FADS (rs1535 and rs174448), PPARG2 (rs1801282), PPARA (rs1800206) and APOE (rs7412+rs429358). Carriage of two FADS rs174448 major alleles was associated with lower TAG (P = 0·027) and higher HDL-cholesterol (P = 0·047). Blood n-3 LCPUFA was inversely associated with TAG and insulin in PPARG2 minor allele carriers and positively with LDL-cholesterol in major allele homozygotes (Pn-3 LCPUFA × rs180182 < 0·01). Associations between n-3 LCPUFA and cardiometabolic markers were not modified by APOE genotype (Pn-3 LCPUFA × APOE > 0·11), but interaction between FADS rs1535 and APOE showed that rs1535 major allele homozygotes who also carried APOE2 had higher HDL-cholesterol than all other genotype combinations (Prs1535 × APOE = 0·019, pairwise-P < 0·05). This indicates that FADS genotypes, which increase endogenous LCPUFA production, may beneficially affect children's cardiometabolic profile in a partly APOE-dependent manner. Also, the degree to which children benefit from higher n-3 LCPUFA intake may depend on their PPARG2 genotype.

Exploring the effects of oily fish consumption on measures of acute and long-term stress in healthy 8-9-year-old children: the FiSK Junior randomised trial.

Long-chain n-3 PUFA (n-3 LCPUFA) are known to reduce blood pressure (BP), heart rate and vagal tone, but potential stress-mitigating effects of n-3 LCPUFA are not well investigated. We explored the effects of oily fish consumption on long-term stress and the stress response in schoolchildren. Healthy 8-9-year-old children were randomised to receive about 300 g/week of oily fish or poultry for 12 weeks (199 randomised, 197 completing). At baseline and endpoint, we measured erythrocyte n-3 LCPUFA, hair cortisol and the response to a 1-min cold pressor test (CPT) on saliva cortisol, BP and continuous electrocardiogram recordings. Post-intervention hair cortisol did not differ between the groups, but sex-specificity was indicated (Psex × group = 0·074, boys: -0·9 (95 % CI -2·9, 1·0) ng/g, girls: 0·7 (95 % CI -0·2, 1·6) ng/g). Children in the fish group tended to be less prone to terminate CPT prematurely (OR 0·20 (95 % CI 0·02, 1·04)). Mean heart beat interval during CPT was 18·2 (95 % CI 0·3, 36·6) ms longer and high frequency power increased (159 (95 % CI 29, 289) ms2) in the fish v. poultry group. The cardiac autonomic response in the 10 min following CPT was characterised by a sympathetic peak followed by a parasympathetic peak, which was most pronounced in the fish group. This exploratory study does not support a strong effect of oily fish consumption on stress but indicates that oily fish consumption may increase vagal cardiac tone during the physiological response to CPT. These results warrant further investigation.

Sleep and physical activity in healthy 8-9-year-old children are affected by oily fish consumption in the FiSK Junior randomized trial.

PURPOSE: Studies indicate that long-chain n-3 PUFA (n-3LCPUFA) affect sleep and physical activity (PA) in childhood. However, few studies used objective tools and none studies examined the effect of fish per se. We aimed to explore if fish consumption affected sleep and PA assessed by accelerometry in children, and if effects were modified by sex. METHODS: In a randomized 12-week trial, 199 healthy 8-9-year-old children received ~ 300 g/week of oily fish or poultry. Sleep and PA were pre-specified explorative outcomes examined by accelerometers that the children wore on their hip for 7 days at baseline and endpoint, while parents registered sleep. Compliance was verified by erythrocyte n-3LCPUFA. RESULTS: The children slept 9.4 ± 0.5 h/night but the sleep duration variability across the week was 6.0 (95%CI: 0.8, 11.1) min lower in the fish vs poultry group. Furthermore, children in the fish group exhibited increased spare time sedentary activity [9.4 (95%CI: 1.8, 16.9) min/day] at the expense of light PA [- 8.2 (95%CI: - 14.4, - 2.0) min/day]. These effects were supported by dose-dependency with n-3LCPUFA. Additionally, latency to sleep onset was reduced by 3.6 (95%CI: 1.0, 6.3) min on weekends and moderate-vigorous PA during school hours was 3.5 (95%CI: 0.1, 6.8) min longer in fish vs poultry. P values for sex interactions were all > 0.05 but the effects tended to be most pronounced on sleep in girls and PA in boys. CONCLUSION: Oily fish intake altered sleep and PA patterns among healthy schoolchildren, with some slight indications of sex differences. These findings warrant further investigation. CLINICAL TRIAL REGISTRY: At clinicaltrials.gov (NCT02809508) and a published protocol in Trials [Damsgaard et al. in Trials, 2016].

Breast milk n-3 long-chain polyunsaturated fatty acids and blood pressure: an individual participant meta-analysis.

PURPOSE: It is controversial whether a higher intake of n-3 long-chain polyunsaturated fatty acids (n-3 LC PUFA) through breastfeeding is associated or not to a lower blood pressure (BP) during childhood. We aimed to clarify this point by undertaking a meta-analysis involving the data from seven European birth cohorts. METHODS: We searched https://www.birthcohort.net for studies that had collected breast milk samples, and had at least one BP measurement in childhood. Principal investigators were contacted, and all agreed to share data. One additional study was identified by contacts with the principal investigators. For each cohort, we analyzed the association of breast milk n-3 LC PUFAs with systolic and diastolic BP with linear mixed effects models or linear regression, and pooled the estimates with a random effects model. We also investigated age-specific and sex-specific associations. RESULTS: A total of 2188 participants from 7 cohorts were included. Overall, no associations between breast milk n-3 LC PUFAs and BP were observed. In the pooled analysis, each 0.1 wt% increment in breast milk docosahexaenoic acid (DHA) was associated with a 1.19 (95% CI - 3.31, 0.94) mmHg lower systolic BP. Associations were similar for boys and girls and at different ages. CONCLUSION: In this individual participant meta-analysis, we found no evidence for an association between breast milk n-3 LC PUFAs and BP.

Sagittal abdominal diameter and waist circumference appear to be equally good as identifiers of cardiometabolic risk.

BACKGROUND AND AIMS: Body mass index (BMI) and waist circumference (WC) are commonly used markers of cardiometabolic risk. However, sagittal abdominal diameter (SAD) has been proposed as a possibly more sensitive marker of intra-abdominal obesity. We investigated differences in how SAD, WC, and BMI were correlated with cardiometabolic risk markers. METHODS AND RESULTS: This cross-sectional study investigated anthropometric and metabolic baseline measurements of individuals from six trials. Multiple linear regression and (partial) correlation coefficients were used to investigate associations between SAD, WC, and BMI and cardiometabolic risk markers, including components of the metabolic syndrome as well as insulin resistance, blood lipids, and lowgrade inflammation. In total 1516 mostly overweight or obese individuals were included in the study. SAD was significantly more correlated with TG than WC for all studies, and overall increase in correlation was 0.05 (95% CI (0.02; 0.08). SAD was significantly more correlated with the markers TG and DBP 0.11 (95% CI (0.08, 0.14)) and 0.04 (95% CI (0.006, 0.07), respectively compared to BMI across all or most studies. CONCLUSION: This study showed that no single anthropometric indicator was consistently more strongly correlated across all markers of cardiometabolic risk. However, SAD was significantly more strongly correlated with TG than WC and significantly more strongly correlated with DBP and TG than BMI.

Fish Oil Supplementation in Pregnancy and Neurodevelopment in Childhood-A Randomized Clinical Trial.

A double-blind randomized controlled trial of n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation or matching placebo during third trimester of pregnancy was conducted within the COPSAC2010 mother-child cohort consisting of 736 women and their children. The objective was to determine if maternal n-3 LCPUFA pregnancy supplementation affects offspring neurodevelopment until 6 years. Neurodevelopment was evaluated in 654 children assessing age of motor milestone achievement, language development, cognitive development, general neurodevelopment, and emotional and behavioral problems. Maternal n-3 LCPUFA supplementation during pregnancy improved early language development and reduced the impact of emotional and behavioral problems. The n-3 LCPUFA supplementation was in boys associated with the earlier achievement of gross motor milestones, improved cognitive development, and a reduced impact of emotional and behavioral problems.

Vitamin D-related genes and cardiometabolic markers in healthy children: a Mendelian randomisation study.

Observational studies show associations between low serum 25-hydroxyvitamin D (25(OH)D) and cardiometabolic risk markers. This Mendelian randomisation study examined associations between cardiometabolic markers in children and SNP in genes related to vitamin D metabolism (DHCR7; group-specific complement (GC); cytochrome P450 subfamily IIR1 (CYP2R1); and CYP24A1) and action (CYP27B1 and VDR). In 699 healthy 8-11-year-old children, we genotyped eleven SNP. We generated a genetic risk score based on SNP associated with low 25(OH)D and investigated associations between this and blood pressure, plasma lipids and insulin. Furthermore, we examined whether SNP related to vitamin D actions modified associations between 25(OH)D and the cardiometabolic markers. All GC and CYP2R1 SNP influenced serum 25(OH)D. A risk score based on four of the six SNP was associated with 3·4 (95 % CI 2·6, 4·2) mmol/l lower 25(OH)D per risk allele (P < 0·001), but was not associated with the cardiometabolic markers. However, interactions were indicated for the three VDR SNP (Pinteraction < 0·081) on associations between 25(OH)D and TAG, systolic blood pressure and insulin, which all decreased with increasing 25(OH)D only in major allele homozygotes (ß -0·02 (95 % CI -0·04, -0·01) mmol/l; ß -0·5 (95 % CI -0·9, -0·1) mmHg; and ß -0·5 (95 % CI -1·4, 0·3) pmol/l, respectively). In conclusion, genetic variation affected 25(OH)D substantially, but the genetic score was not associated with cardiometabolic markers in children. However, VDR polymorphisms modified associations with vitamin D, which warrants further investigation of VDR's role in the relationship between vitamin D and cardiometabolic risk.

Is high oily fish intake achievable and how does it affect nutrient status in 8-9-year-old children?: the FiSK Junior trial.

PURPOSE: Most children do not meet dietary guidelines for fish intake. Fish is the main source of EPA (20:5n-3), DHA (22:6n-3) and vitamin D, but may replace better iron sources such as meat. We investigated if intake of 300 g/week oily fish was achievable in children and how it affected their nutrient status. Additionally, we validated a fish food frequency questionnaire (FFQ) by correlations against EPA + DHA in red blood cells (RBC). METHODS: In a randomised 12-week trial, 199 children (8-9 years) received oily fish or poultry (control) to be eaten five times/week. We measured dietary intake and analysed fasting RBC EPA + DHA, serum 25-hydroxyvitamin D (25(OH)D), blood haemoglobin and plasma ferritin. RESULTS: 197 (99%) children completed the study. The median (25th-75th percentile) intake was 375 (325-426) and 400 (359-452) g/week oily fish and poultry, respectively. The fish group increased their intake of EPA + DHA by 749 (593-891) mg/day and vitamin D by 3.1 (1.6-3.8) µg/day. Endpoint RBC EPA + DHA was 2.3 (95% CI 1.9; 2.6) fatty acid %-point higher than the poultry group (P < 0.001). The fish group avoided the expected 25(OH)D winter decline (P < 0.001) and had 23%-point less vitamin D insufficiency (winter subgroup, n = 82). Haemoglobin and ferritin decreased slightly in both groups (P < 0.05), but the number of children with low values did not change (P > 0.14). FFQ estimates moderately reflected habitual intake (r = 0.28-0.35) and sufficiently captured intervention-introduced changes in intake (r > 0.65). CONCLUSION: Oily fish intake of 300 g/week was achievable and improved children's EPA + DHA and 25(OH)D status, without markedly compromising iron status. These results justify public health initiatives focusing on children's fish intake.

Whole-blood PUFA and associations with markers of nutritional and health status in acutely malnourished children in Cambodia.

OBJECTIVE: To measure fatty acid composition, particularly whole-blood PUFA content, in acutely malnourished children and identify associations with markers of nutritional and health status. DESIGN: PUFA were assessed in dried blood spots obtained from a cross-sectional study. Nutritional and health status were assessed by anthropometry, haemoglobinopathies, inflammation and blood counts. SETTING: Cambodia. PARTICIPANTS: The study was conducted with 174 children aged 0·5-18 years with acute malnutrition. RESULTS: Among total fatty acids (FA), the relative percentage of total PUFA was 20 % FA, with 14 % of the children having very low PUFA (mead acid (MA):arachidonic acid (AA) >0·02, n-6 docosapentaenoic acid:DHA >0·2 and total n-6:n-3 PUFA >10·5). Wasting was not associated with any PUFA. Stunting and low height were consistently positively associated with total PUFA and positively with n-6 PUFA. Height was positively associated with n-3 long-chain PUFA (LCPUFA). The presence of haemoglobinopathies or inflammation was positively associated with MA:AA, but not total PUFA. Elevated blood platelet counts were positively correlated with linoleic acid and appeared to be influenced by anaemia (P = 0·010) and inflammation (P = 0·002). Monocyte counts were high during inflammation (P = 0·052) and correlated positively with n-6 LCPUFA and n-3 LCPUFA. CONCLUSIONS: Children with acute malnutrition or stunting had low PUFA, while elevated platelets and monocytes were associated with high PUFA. In acutely malnourished children, inflammation could lead to elevated blood cell counts resulting in increased whole-blood PUFA which does not reflect dietary intake or nutritional status.

Early development in children with moderate acute malnutrition: A cross-sectional study in Burkina Faso.

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health-related correlates. This cross-sectional study used baseline data from a nutritional trial in children with MAM aged 6-23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio-economic status, anthropometry, body composition, whole-blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z-scores were -0.39 (-0.45, -0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and -0.91 (-0.96, -0.86) for language skills. Children with higher mid-upper arm circumference, weight-for-height, height-for-age, fat-free mass, n-3 PUFAs, Hb, and iron status had better MDAT z-scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z-scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z-scores. Associations between morbidity and z-scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.

OBJECTIVE: To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN: 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. RESULTS: 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. CONCLUSION: Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation. TRIAL REGISTRATION NUMBER: NCT01731366; Results.

FADS and PPARG2 Single Nucleotide Polymorphisms are Associated with Plasma Lipids in 9-Mo-Old Infants.

BACKGROUND: Dietary intake of polyunsaturated fatty acids (PUFAs), e.g., linoleic acid and n-3 (ω-3) long-chain PUFAs, has been shown in adults to affect plasma cholesterol and triglycerides (TGs), respectively. Little is known about the effects of PUFAs on plasma lipids in early life. OBJECTIVE: The aim of this study was to explore the associations between plasma concentrations of total, LDL, and HDL cholesterol and TGs in infants and 2 single nucleotide polymorphisms (SNPs) in the fatty acid desaturase genes (FADS) oppositely associated with docosahexaenoic acid (rs1535 and rs174448) and potential effect modification by a functional peroxisome proliferator-activated receptor-γ2 gene variant (PPARG2 Pro12Ala). METHODS: In 9-mo-old infants (n = 561) from 3 Danish cohorts, we analyzed associations between plasma lipids, erythrocyte PUFAs, and FADS SNPs, and interactions with PPARG2 Pro12Ala genotype, by multiple linear regression. We also examined potential effect modification by breastfeeding, as 46% of the infants were still being breastfed. RESULTS: Minor allele carriage of rs174448 was associated with lower total cholesterol (difference: -0.22 mmol/L; 95% CI: -0.37, -0.06 mmol/L; P = 0.006) and LDL cholesterol (difference: -0.15 mmol/L; 95% CI: -0.29, -0.01 mmol/L; P = 0.035), but no associations were observed with TGs or for rs1535. Minor allele carriage of both FADS SNPs was associated with 1 SD lower HDL cholesterol, but only in currently breastfed infants (rs174448 × breastfeeding, P = 0.080; rs1535 × breastfeeding, P = 0.030) and PPARG2 minor allele carriers (rs174448 × PPARG2, P = 0.001; rs1535 × PPARG2, P = 0.004). Erythrocyte arachidonic acid and eicosapentaenoic acid were inversely associated with LDL cholesterol [estimated effect (ß): -0.3 mmol/L; 95% CI: -0.06, -0.00 mmol/L per percentage of fatty acids (FA%); P = 0.035] and TGs (ß: -0.23 mmol/L; 95% CI: -0.41, -0.05 mmol/L per FA%; P = 0.015), respectively. CONCLUSIONS: The observed associations with FADS variants indicate that PUFAs are involved in plasma lipid regulation in 9-mo-old infants. Observed FADS SNP differences and interactions with breastfeeding and PPARG2 warrant additional studies to explore the effects of individual FADS SNPs on PUFA status and potential genetic modification of dietary PUFA effects.

Determinants of neurodevelopment in early childhood - results from the Copenhagen prospective studies on asthma in childhood (COPSAC2010 ) mother-child cohort.

AIM: The objective of this study was to identify possible pre- and postnatal factors influencing neurodevelopment of the young child. METHODS: We used data from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010 ) mother-child cohort, but excluded those with a neurological diagnosis, born <37 weeks of gestation and birthweights <2500 g, resulting in 650 children analysed. Neurodevelopment was assessed as age of achievement of early milestones, language scores at 1 and 2 years and cognitive score at 2 ½ years of age. RESULTS: Neurodevelopmental scores were not associated with breastfeeding, persistent wheeze, eczema and number of sick days (p > 0.05 in all tests). Early age at milestone achievement was associated with male sex (p = 0.05), lower maternal age (p = 0.02), higher gestational age (p < 0.001) and paternity leave (p = 0.01). A higher 1-year language score was associated with female sex (p = 0.02) and maternal smoking during pregnancy (p = 0.01) and a higher 2-year language score with female sex (p < 0.001) and being first born (p = 0.01). A higher cognitive score was associated with female sex (p = 0.02). CONCLUSION: Neurodevelopmental scores were unrelated to breastfeeding, persistent wheeze, eczema and number of sick days. Neurodevelopment in early childhood was mostly associated with gender.

Physical activity level among children recovering from severe acute malnutrition.

OBJECTIVE: To assess the level and predictors of physical activity at discharge among children recovering from severe acute malnutrition (SAM). METHODS: We conducted a prospective study among 69 children 6-59 months of age admitted with SAM for nutritional rehabilitation at Mulago National Referral Hospital, Uganda. Using hip-mounted triaxial accelerometers, we measured physical activity expressed as counts per minute (cpm) during the last three days of hospital treatment. As potential predictors, we assessed clinical and background characteristics, duration to transition phase and duration of hospitalisation, serum C-reactive protein and whole-blood docosahexaenoic acid (DHA). Multiple linear regression analyses were used to identify predictors of physical activity. RESULTS: The median (IQR) age was 15.5 (12.6; 20.5) months. At discharge, the mean (SD) movement was 285 (126) cpm. Physical activity was 43 (19; 67) cpm higher for each unit increase in weight-for-height z-score (WHZ) and 72 (36; 108) cpm higher for each centimetre increase in MUAC. Whole-blood DHA on admission was also a positive predictor of physical activity, whereas duration to transition phase and duration of hospitalisation were both negative predictors. CONCLUSION: The level of physical activity at discharge among children treated for SAM was low. WHZ, MUAC and DHA on admission were positive predictors of physical activity, whereas duration of stabilisation and hospitalisation was negative predictors of physical activity. These results suggest that assessment of physical activity may be used as a marker of recovery.