Comparison of Omega-3 Eicosapentaenoic Acid Versus Docosahexaenoic Acid-Rich Fish Oil Supplementation on Plasma Lipids and Lipoproteins in Normolipidemic Adults.

BACKGROUND: Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have both shared and different cardiovascular effects, and commonly used fish oil supplements have considerably varied EPA/DHA ratios. AIMS: We compared the effects of fish oil supplements with different EPA/DHA ratios on lipoprotein metabolism. METHODS: In a double-blind, randomized cross-over study, normolipidemic adults (n = 30) consumed 12 g/day of EPA-rich (EPA/DHA: 2.3) or DHA-rich (EPA/DHA: 0.3) fish oil for 8-weeks, separated by an 8-week washout period. RESULTS: Both fish oil supplements similarly lowered plasma TG levels and TG-related NMR parameters versus baseline (p < 0.05). There were no changes in plasma cholesterol-related parameters due to either fish oil, although on-treatment levels for LDL particle number were slightly higher for DHA-rich oil compared with EPA-rich oil (p < 0.05). Both fish oil supplements similarly altered HDL subclass profile and proteome, and down regulated HDL proteins related to inflammation, with EPA-rich oil to a greater extent. Furthermore, EPA-rich oil increased apoM abundance versus DHA-rich oil (p < 0.05). CONCLUSIONS: Overall, fish oil supplements with varied EPA/DHA ratios had similar effects on total lipids/lipoproteins, but differences were observed in lipoprotein subfraction composition and distribution, which could impact on the use of EPA versus DHA for improving cardiovascular health.

Supplementation with saury oil, a fish oil high in omega-11 monounsaturated fatty acids, improves plasma lipids in healthy subjects.

BACKGROUND: Fish oil enriched in omega-11 long-chain monounsaturated fatty acids (LCMUFAs; C20:1 and C22:1 isomers combined) have shown lipid-lowering and atheroprotective effects in animal models. OBJECTIVE: To perform a first-in-human trial of LCMUFA-rich saury fish oil supplementation to test its safety and possible effect on plasma lipids. METHODS: A double-blind, randomized, crossover clinical trial was carried out in 30 healthy normolipidemic adults (BMI <25 kg/m2; mean TG, 84 mg/dL). Treatment periods of 8 weeks were separated by an 8-week washout period. Subjects were randomized to receive either 12 g of saury oil (3.5 g of LCMUFA and 3.4 g of omega-3 FAs) or identical capsules with control oil (a mixture of sardine and olive oil; 4.9 g of shorter-chain MUFA oleate and 3 g of omega-3 FAs). RESULTS: Saury oil supplementation was safe and resulted in LDL particle counts 12% lower than control oil (P < .001). Saury oil also had a minor effect on increasing HDL particle size (9.8 nm vs 9.7 nm; P < .05) based on a linear mixed effect model. In contrast, control oil, but not saury oil, increased LDL-C by 7.5% compared with baseline (P < .05). Saury oil had similar effects compared with control oil on lowering plasma TG levels, VLDL, and TG-rich lipoprotein particle counts (by ∼16%, 25%, and 35%, respectively; P < .05), and increasing HDL-C and cholesterol efflux capacity (by ∼6% and 8%, respectively; P < .05) compared with baseline. CONCLUSION: Saury oil supplementation is well tolerated and has beneficial effects on several cardiovascular parameters, such as LDL particle counts, HDL particle size, and plasma TG levels.

Canagliflozin triggers the FGF23/1,25-dihydroxyvitamin D/PTH axis in healthy volunteers in a randomized crossover study.

BACKGROUND: Sodium glucose cotransporter-2 (SGLT2) inhibitors are the most recently approved class of drugs for type 2 diabetes and provide both glycemic efficacy and cardiovascular risk reduction. A number of safety issues have been identified, including treatment-emergent bone fractures. To understand the overall clinical profile, these safety issues must be balanced against an attractive efficacy profile. Our study was designed to investigate pathophysiological mechanisms mediating treatment-emergent adverse effects on bone health. METHODS: We conducted a single-blind randomized crossover study in hospitalized healthy adults (n = 25) receiving either canagliflozin (300 mg/d) or placebo for 5 days. The primary end-point was the drug-induced change in AUC for plasma intact fibroblast growth factor 23 (FGF23) immunoactivity between 24 and 72 hours. RESULTS: Canagliflozin administration increased placebo-subtracted mean levels of serum phosphorus (+16%), plasma FGF23 (+20%), and plasma parathyroid hormone (PTH) (+25%), while decreasing the level of 1,25-dihydroxyvitamin D (-10%). There was substantial interindividual variation in the magnitude of each of these pharmacodynamic responses. The increase in plasma FGF23 was correlated with the increase in serum phosphorus, and the decrease in plasma 1,25-dihydroxyvitamin D was correlated with the increase in plasma FGF23. CONCLUSIONS: Canagliflozin induced a prompt increase in serum phosphorus, which triggers downstream changes in FGF23, 1,25-dihydroxyvitamin D, and PTH, with potential to exert adverse effects on bone health. These pharmacodynamic data provide a foundation for future research to elucidate pathophysiological mechanisms of adverse effects on bone health, with the objective of devising therapeutic strategies to mitigate the drug-associated fracture risk. TRIAL REGISTRATION: ClinicalTrial.gov (NCT02404870). FUNDING: Supported by the Intramural Program of NIDDK.

Mindfulness and laboratory eating behavior in adolescent girls at risk for type 2 diabetes.

Mindfulness-based intervention has become increasingly popular to address disinhibited eating in obesity and type 2 diabetes (T2D). Theoretically, present-moment attention promotes the ability to recognize and respond to internal hunger cues and to differentiate physiological hunger from other stimuli. Yet, there is limited research describing the relationship of mindfulness with disinhibited eating patterns in adolescents. In this study, we evaluated the relationship of dispositional mindfulness to laboratory eating in 107 adolescent (12-17 years) girls at risk for T2D. Adolescents reported dispositional mindfulness, were evaluated for recent loss-of-control-eating (LOC-eating) by interview, and participated in two successive, standardized laboratory test meals to assess eating when hungry as well as eating in the absence of hunger (EAH). Adolescents rated state appetite throughout the test meal paradigms. In analyses adjusting for body composition and other possible confounds, mindfulness was inversely related to caloric intake during the EAH paradigm. Mindfulness did not relate to energy intake when hungry. Instead, there was a significant interaction of reported LOC-eating by state hunger, such that girls with recent, reported LOC-eating and high state hunger consumed more calories when hungry, regardless of mindfulness. Findings suggest that in girls at risk for T2D, mindfulness may play a role in disinhibited eating. A propensity for LOC-eating may be most salient for overeating in a high hunger state.

Mindfulness and eating behavior in adolescent girls at risk for type 2 diabetes.

OBJECTIVE: The purpose of this investigation was to examine the relationship of dispositional mindfulness to binge eating and associated eating attitudes and behaviors among adolescent girls at risk for type 2 diabetes (T2D). METHODS: Participants were 114 overweight or obese adolescents enrolled in a study of girls with a family history of T2D and mild depressive symptoms. Adolescent self-reports of mindfulness, eating in the absence of hunger, and depressive symptoms were collected. An interview was administered to determine presence of binge eating episodes and a behavioral task was used to assess the reinforcing value of food relative to other nonsnack food rewards. Body composition was assessed using dual-energy X-ray absorptiometry. RESULTS: In analyses accounting for race, percent body fat, lean mass, height, age, and depressive symptoms, dispositional mindfulness was associated with a lower odds of binge eating (p = .002). Controlling for the same potential confounds, mindfulness was also inversely associated with eating concern, eating in the absence of hunger in response to fatigue/boredom, and higher food reinforcement relative to physical activity (all p < .05). DISCUSSION: In girls with a family history of T2D, independent of body composition and depressive symptoms, intraindividual differences in mindfulness are related to binge eating and associated attitudes and behaviors that may confer risk for obesity and metabolic problems. Further research is needed to determine the extent to which mindfulness plays a role in the etiology and/or maintenance of disinhibited eating in adolescents at risk for T2D.

Diet-induced changes in n-3- and n-6-derived endocannabinoids and reductions in headache pain and psychological distress.

UNLABELLED: Omega-3 and omega-6 fatty acids are biosynthetic precursors of endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation-increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)-reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (N = 55) to investigate 1) whether the H3-L6 intervention altered omega-3- and omega-6-derived endocannabinoids in plasma and 2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, P < .001) and docosahexaenoylethanolamine (+99%, P < .001) and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, P = .001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01157208) PERSPECTIVE: This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related conditions.

Maternal consumption of a DHA-containing functional food benefits infant sleep patterning: an early neurodevelopmental measure.

BACKGROUND: Docosahexaenoic acid (DHA; 22:6n-3) is highly important during pregnancy for optimal development and functioning of fetal neural tissue. Infant ability to organize sleep and wake states following parturition is highly associated with later developmental outcomes. The impact of maternal DHA intake on sleep organization has not been previously investigated. AIMS: To examine the effect of a DHA-containing functional food consumed during pregnancy on early neurobehavioral development as assessed by infant sleep patterning in the first 48 postnatal hours. STUDY DESIGN: A longitudinal, randomized, double-blinded, placebo-controlled design was used. SUBJECTS: Women (18-35 y) with no pregnancy complications consumed a cereal-based functional food (92 kcal) containing 300 mg DHA an average of 5 d/week or placebo bars (n=27 DHA, n=21 Placebo). The intervention began at 24 weeks gestation and continued until delivery (38-40 weeks). OUTCOME MEASURES: Infant sleep/wake states were measured on postnatal days 1 (D1) and 2 (D2) using a pressure sensitive mattress recording respiration and body movements. RESULTS: Using ANCOVA and controlling for ethnic variation, there were significant group differences in arousals in quiet sleep on D1 (P=0.006) and D2 (P=0.011) with fewer arousals in the DHA intervention group compared to the placebo group. Similarly, arousals in active sleep on D1 were significantly lower in the DHA-intervention group (P=0.012) compared to the placebo group. CONCLUSIONS: We conclude that increased prenatal supply of dietary DHA has a beneficial impact on infant sleep organization.