Dietary n-3 alpha-linolenic and n-6 linoleic acids modestly lower serum lipoprotein(a) concentration but differentially influence other atherogenic lipoprotein traits: A randomized trial.

BACKGROUND AND AIMS: Lipoprotein(a) [Lp(a)] is a causal, genetically determined cardiovascular risk factor. Limited evidence suggests that dietary unsaturated fat may increase serum Lp(a) concentration by 10-15 %. Linoleic acid may increase Lp(a) concentration through its endogenous conversion to arachidonic acid, a process regulated by the fatty acid desaturase (FADS) gene cluster. We aimed to compare the Lp(a) and other lipoprotein trait-modulating effects of dietary alpha-linolenic (ALA) and linoleic acids (LA). Additionally, we examined whether FADS1 rs174550 genotype modifies Lp(a) responses. METHODS: A genotype-based randomized trial was performed in 118 men homozygous for FADS1 rs174550 SNP (TT or CC). After a 4-week run-in period, the participants were randomized to 8-week intervention diets enriched with either Camelina sativa oil (ALA diet) or sunflower oil (LA diet) 30-50 mL/day based on their BMI. Serum lipid profile was measured at baseline and at the end of the intervention. RESULTS: ALA diet lowered serum Lp(a) concentration by 7.3 % (p = 0.003) and LA diet by 9.5 % (p < 0.001) (p = 0.089 for between-diet difference). Both diets led to greater absolute decreases in individuals with higher baseline Lp(a) concentration (p < 0.001). Concentrations of LDL cholesterol (LDL-C), non-HDL-C, remnant-C, and apolipoprotein B were lowered more by the ALA diet (p < 0.01). Lipid or lipoprotein responses were not modified by the FADS1 rs174550 genotype. CONCLUSIONS: A considerable increase in either dietary ALA or LA from vegetable oils has a similar Lp(a)-lowering effect, whereas ALA may lower other major atherogenic lipids and lipoproteins to a greater extent than LA. Genetic differences in endogenous PUFA conversion may not influence serum Lp(a) concentration.

Associations of diet quality and food consumption with serum biomarkers for lipid and amino acid metabolism in Finnish children: the PANIC study.

PURPOSE: To investigate the associations of overall diet quality and dietary factors with serum biomarkers for lipid and amino acid metabolism in a general population of children. METHODS: We studied 194 girls and 209 boys aged 6-8 years participating in the Physical Activity and Nutrition in Children study. Food consumption was assessed by 4-day food records and diet quality was quantified by the Finnish Children Healthy Eating Index (FCHEI). Fasting serum fatty acids, amino acids, apolipoproteins, as well as lipoprotein particle sizes were analyzed with high-throughput nuclear magnetic resonance spectroscopy. Data were analyzed using linear regression adjusted for age, sex, and body fat percentage. RESULTS: FCHEI was directly associated with the ratio of polyunsaturated (PUFA) to saturated fatty acids (SFA) (PUFA/SFA), the ratio of PUFA to monounsaturated fatty acids (MUFA) (PUFA/MUFA), the ratio of PUFA to total fatty acids (FA) (PUFA%), the ratio of omega-3-fatty acids to total FA (omega-3 FA%), and inversely associated with the ratio of MUFA to total FA (MUFA%), alanine, glycine, histidine and very-low density lipoprotein (VLDL) particle size. Consumption of vegetable oils and vegetable-oil-based margarine (≥ 60% fat) was directly associated with PUFA/SFA, PUFA/MUFA, PUFA%, the ratio of omega-6 FA to total FA (omega-6 FA%), and inversely associated with SFA, MUFA, SFA to total FA (SFA%), MUFA%, alanine and VLDL particle size. Consumption of high-fiber grain products directly associated with PUFA/SFA, PUFA/MUFA, omega-3 FA%, omega-6 FA%, PUFA% and inversely associated with SFA and SFA%. Fish consumption directly related to omega-3 FA and omega-3 FA%. Consumption of sugary products was directly associated with histidine and VLDL particle size. Vegetable, fruit, and berry consumption had direct associations with VLDL particle size and the ratio of apolipoprotein B to apolipoprotein A1. Consumption of low fat (< 1%) milk was directly associated with phenylalanine. A higher consumption of high-fat (≥ 1%) milk was associated with lower serum MUFA/SFA and higher SFA%. Sausage consumption was directly related to SFA% and histidine. Red meat consumption was inversely associated with glycine. CONCLUSIONS: Better diet quality, higher in intake of dietary sources of unsaturated fat and fiber, and lower in sugary product intake were associated with more favorable levels of serum biomarkers for lipid and amino acid metabolism independent of adiposity. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01803776, registered March 3, 2013.

Effects of 2-year dietary and physical activity intervention on cognition in children-a nonrandomized controlled trial.

BACKGROUND AND OBJECTIVE: We investigated the effects of a combined dietary and PA intervention on cognition in children and whether changes in diet quality, PA, sedentary behavior (SB), and sedentary time (ST) are associated with changes in cognition. METHODS: We conducted a 2-year nonrandomized controlled trial in 504 children aged 6-9 years at baseline. The children were allocated to a combined dietary and PA intervention group (n = 237) or a control group (n = 160) without blinding. INTERVENTIONS: The children and their parents allocated to the intervention group had six dietary counseling sessions of 30-45 min and six PA counseling sessions of 30-45 min during the 2-year intervention period. The children were also encouraged to participate in after-school exercise clubs. Cognition was assessed by the Raven's Colored Progressive Matrices. We assessed dietary factors by 4 days food records and computed the Baltic Sea Diet Score (BSDS) as a measure of diet quality. PA and ST were assessed by a combined heart rate and body movement monitor, types of PA and SB by a questionnaire. RESULTS: The intervention had no effect on cognition. Increased BSDS and consumption of low-fat milk and decreased consumption of red meat and sausages were associated with improved cognition over 2 years. Increased organized sports, ST, and reading were positively, while unsupervised PA, computer use, and writing were negatively associated with cognition. CONCLUSION: Combined dietary and PA intervention had no effect on cognition. Improved diet quality and increased organized sports and reading were associated with improved cognition.

The FADS1 rs174550 Genotype Modifies the n-3 and n-6 PUFA and Lipid Mediator Responses to a High Alpha-Linolenic Acid and High Linoleic Acid Diets.

SCOPE: The fatty acid composition of plasma lipids, which is associated with biomarkers and risk of non-communicable diseases, is regulated by dietary polyunsaturated fatty acids (PUFAs) and variants of fatty acid desaturase (FADS). We investigated the interactions between dietary PUFAs and FADS1 rs174550 variant. METHODS AND RESULTS: Participants (n = 118), homozygous for FADS1 rs174550 variant (TT and CC) followed a high alpha-linolenic acid (ALA, 5 percent of energy (E-%)) or a high linoleic acid (LA, 10 E-%) diet during an 8-week randomized controlled intervention. Fatty acid composition of plasma lipids and PUFA-derived lipid mediators were quantified by gas and liquid chromatography mass spectrometry, respectively. The high-LA diet increased the concentration of plasma LA, but not its lipid mediators. The concentration of plasma arachidonic acid decreased in carriers of CC and remained unchanged in the TT genotype. The high-ALA diet increased the concentration of plasma ALA and its cytochrome P450-derived epoxides and dihydroxys, and cyclooxygenase-derived monohydroxys. Concentrations of plasma eicosapentaenoic acid and its mono- and dihydroxys increased only in TT genotype carriers. CONCLUSIONS: These findings suggest the potential for genotype-based recommendations for PUFA consumption, resulting in modulation of bioactive lipid mediators which can exert beneficial effects in maintaining health.

The effects of an 8-year individualised lifestyle intervention on food consumption and nutrient intake from childhood to adolescence: the PANIC Study.

We aimed to investigate the effects of a long-term, individualised, family-based lifestyle intervention on food consumption and nutrient intake from childhood to adolescence. We conducted an 8-year diet and physical activity intervention study in a population sample of children aged 7-9 years at baseline in 2007-2009. We allocated the participants to the intervention group (n 306) and the control group (n 198). We assessed diet by 4-d food records at baseline, 2-year follow-up and 8-year follow-up. We analysed the data using linear mixed-effects models adjusted for age at baseline and sex. The consumption of vegetables and vegetable oil-based spreads (fat ≥60 %) increased in the intervention group but did not change in the control group (P < 0⋅001 for time×group interaction). The consumption of fruits and berries increased in the intervention group but decreased in the control group (P = 0⋅036). The consumption of high-fat cheese (P = 0⋅029), butter-based spreads (P = 0⋅001) and salty snacks (P = 0⋅028) increased less, and the consumption of low-fat cheese (P = 0⋅004) increased more in the intervention group than in the control group. Saturated fat intake (P = 0⋅001) increased less, and the intakes of dietary fibre (P = 0⋅003), vitamin D (P = 0⋅042) and vitamin E (P = 0⋅027) increased more in the intervention group than in the control group. The intakes of vitamin C (P < 0⋅001) and folate (P = 0⋅001) increased in the intervention group but decreased in the control group. To conclude, individualised, family-based lifestyle intervention altered food choices towards more recommended diet and resulted in enhanced diet quality from childhood to adolescence.

Associations of physical activity, sedentary time, and diet quality with biomarkers of inflammation in children.

We investigated the associations of physical activity (PA), sedentary time (ST), and diet quality with biomarkers of inflammation in 390 children (192 girls, 198 boys) aged 6-8 years. PA energy expenditure (PAEE), light PA, moderate PA (MPA), vigorous PA (VPA), moderate-to-vigorous PA (MVPA), and ST were assessed by combined movement and heart rate sensor. Finnish Children Healthy Eating Index was calculated using data from 4 d food records. Body fat percentage (BF%) was measured by dual-energy X-ray absorptiometry. High-sensitivity C-reactive protein (Hs-CRP), leptin, interleukin-6 (IL-6), adiponectin, tumour necrosis factor-α, and glycoprotein acetyls were measured from fasting blood samples. PAEE, MPA, VPA, and MVPA were inversely associated with hs-CRP (ß=-191 to -139, 95% CI=-0.294 to -0.024), leptin (ß=-0.409 to -0.301, 95% CI=-0.499 to -0.107), IL-6 (ß=-0.136 to -0.104, 95% CI=-0.240 to -0.001) and PAEE, MPA, and MVPA were inversely associated with glycoprotein acetyls (ß=-0.117 to -0.103, 95% CI=-0.213 to -0.001). ST was directly associated with hs-CRP (ß=0.170, 95% CI=0.070-0.269), leptin (ß=0.355, 95% CI=0.265-0.445), and IL-6 (ß=0.105, 95% CI=0.005-0.205). VPA was inversely associated with hs-CRP, leptin, and IL-6 in children with higher BF% (ß=-0.344 to -0.181, 95% CI=-0.477 to -0.033) but not among children with lower BF% (ß=-0.007-0.033, 95% CI=-0.183-0.184). In conclusion, PA was inversely and ST directly associated with circulating levels of biomarkers of inflammation among children. Furthermore, we observed that PA was inversely associated with these biomarkers for inflammation in children with a higher BF%. HighlightsSystemic inflammation, as indicated by increased circulating concentrations of biomarkers for inflammation, may be important in causal pathways leading to insulin resistance, sub-clinical atherosclerosis, and eventually clinical manifestations of cardiovascular diseases.Higher levels of physical activity and lower levels of sedentary time were associated with more favourable inflammatory profile.Body fat percentage modified these associations and especially vigorous intensity physical activity was inversely associated with biomarkers of inflammation on children with higher body fat percentage but not in children with lower body fat percentage.

Dietary fat intakes and cardiovascular disease risk in adults with type 2 diabetes: a systematic review and meta-analysis.

PURPOSE: Advice regarding the intake of dietary fats is particularly relevant to those with type 2 diabetes, given their increased risk of cardiovascular disease. METHODS: We have undertaken a systematic review of fat intakes and cardiovascular disease risk in adults with type 2 diabetes using an online search strategy to 24 April 2020, augmented with hand searching. Searches, extraction, and risk of bias assessments were undertaken by two researchers. The quality of evidence was assessed with GRADE protocols. RESULTS: We identified five eligible prospective studies of 22,591 participants followed for on average 9.8 years, and one trial of 14 participants with type 2 diabetes. Limited data were available; however, replacement analyses of saturated fat with polyunsaturated fat (RR for 2% energy replacement 0.87 95% CI: 0.77-0.99) or carbohydrate (RR for 5% energy replacement 0.82 95% CI: 0.67-1.00) was associated with reduced cardiovascular disease occurrence. Higher polyunsaturated: saturated fat intake was also associated with reduced cardiovascular disease occurrence (RR 0.75 95% CI: 0.57-0.98). The quality of evidence was low to very-low. CONCLUSION: Although only limited data were available, replacement of saturated fats with other macronutrients, such as polyunsaturated fats, was associated with reduced cardiovascular disease occurrence. Supporting evidence from research in the general population increases confidence in these findings. Until more data are available to better comment on dietary fat intakes in cardiovascular disease risk of those with type 2 diabetes, it appears appropriate that saturated fats be replaced in the diet with other macronutrients, such as polyunsaturated fats.

The FADS1 Genotype Modifies Metabolic Responses to the Linoleic Acid and Alpha-linolenic Acid Containing Plant Oils-Genotype Based Randomized Trial FADSDIET2.

SCOPE: The article investigates the FADS1 rs174550 genotype interaction with dietary intakes of high linoleic acid (LA) and high alpha-linolenic acid (ALA) on the response of fatty acid composition of plasma phospholipids (PLs), and of markers of low-grade inflammation and glucose-insulin homeostasis. METHODS AND RESULTS: One-hundred thirty homozygotes men for FADS1 rs174550 SNP (TT and CC genotypes) were randomized to an 8-week intervention with either LA- or ALA-enriched diet (13 E% PUFA). The source of LA and ALA are 30-50 mL of sunflower oil (SFO, 62-63% LA) and Camelina sativa oil (CSO, 30- are randomized to an 35% ALA), respectively. In the SFO arm, there is a significant genotype x diet interaction for the proportion of arachidonic acid in plasma phospholipids (p < 0.001), disposition index (DI30 ) (p = 0.039), and for serum high-sensitive c-reactive protein (hs-CRP, p = 0.029) after excluding the participants with hs-CRP concentration of >10 mg L-1 and users of statins or anti-inflammatory therapy. In the CSO arm, there are significant genotype x diet interactions for n-3 polyunsaturated fatty acids, but not for the clinical characteristics. CONCLUSIONS: The FADS1 genotype modifies the response to high PUFA diets, especially to high-LA diet. These findings suggest that approaches considering FADS variation may be useful in personalized dietary counseling.

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.

"notame": Workflow for Non-Targeted LC-MS Metabolic Profiling.

Metabolomics analysis generates vast arrays of data, necessitating comprehensive workflows involving expertise in analytics, biochemistry and bioinformatics in order to provide coherent and high-quality data that enable discovery of robust and biologically significant metabolic findings. In this protocol article, we introduce notame, an analytical workflow for non-targeted metabolic profiling approaches, utilizing liquid chromatography-mass spectrometry analysis. We provide an overview of lab protocols and statistical methods that we commonly practice for the analysis of nutritional metabolomics data. The paper is divided into three main sections: the first and second sections introducing the background and the study designs available for metabolomics research and the third section describing in detail the steps of the main methods and protocols used to produce, preprocess and statistically analyze metabolomics data and, finally, to identify and interpret the compounds that have emerged as interesting.

Child-related and parental predictors for thelarche in a general population of girls: the PANIC study.

BACKGROUND: Obesity has been associated with earlier thelarche, whereas other predictors for it remain unclear. METHODS: We studied child-related and parental predictors for earlier thelarche in 195 girls aged 6-8 years followed up for 2 years. A physician evaluated breast development by inspection and palpation. Body fat percentage (BF%) was measured by dual-energy X-ray absorptiometry, diet by food records, and physical activity and sedentary time by body movement and heart rate monitors. Parental education, smoking, and alcohol consumption and household income were assessed by questionnaires. Gestational age, birth weight, and maternal prepregnancy BMI were obtained from hospital registers. Predictors for thelarche were examined using logistic regression analysis adjusted for age and follow-up time. RESULTS: The incidence of thelarche during 2 years increased by 11% (OR 1.11, CI 1.06-1.17, p < 0.001) for 1 unit increase in baseline BF%. Girls with a smoking parent had a 2.64 (95% CI 1.21-5.77, p = 0.015) times higher incidence of thelarche than other girls. The associations of lower parental education and higher maternal prepregnancy BMI with the higher incidence of thelarche were largely explained by BF%. Other possible predictors were not associated with thelarche. CONCLUSIONS: Higher BF% and exposure to tobacco smoke are independent predictors for earlier thelarche.