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Background: Omega-3 polyunsaturated fatty acids (PUFAs) have been proposed to improve chronic neuroinflammatory diseases in peripheral and central nervous systems. For instance, docosahexaenoic acid (DHA) protects nerve cells from noxious stimuli in vitro and in vivo. Recent reports link PUFA supplementation to improving painful diabetic neuropathy (pDN) symptoms, but cellular mechanisms responsible for this therapeutic effect are not well understood. The objective of this study is to identify distinct cellular pathways elicited by dietary omega-3 PUFA supplementation in patients with type 2 diabetes mellitus (T2DM) affected by pDN., Methods: Forty volunteers diagnosed with type 2 diabetes were enrolled in the "En Balance-PLUS" diabetes education study. The volunteers participated in weekly lifestyle/nutrition education and daily supplementation with 1000 mg DHA and 200 mg eicosapentaenoic acid. The Short-Form McGill Pain Questionnaire validated clinical determination of baseline and post-intervention pain complaints. Laboratory and untargeted metabolomics analyses were conducted using blood plasma collected at baseline and after three months of participation in the dietary regimen. The metabolomics data were analyzed using random forest, hierarchical clustering, ingenuity pathway analysis, and metabolic pathway mapping., Results: The data show that metabolites involved in oxidative stress and glutathione production shifted significantly to a more anti-inflammatory state post supplementation. Example of these metabolites include cystathionine (+90%), S-methylmethionine (+9%), glycine cysteine-glutathione disulfide (+157%) cysteinylglycine (+19%), glutamate (-11%), glycine (+11%), and arginine (+13.4%). In addition, the levels of phospholipids associated with improved membrane fluidity such as linoleoyl-docosahexaenoyl-glycerol (18:2/22:6) (+253%) were significantly increased. Ingenuity pathway analysis suggested several key bio functions associated with omega-3 PUFA supplementation such as formation of reactive oxygen species ( p = 4.38 × 10 -4 , z-score = -1.96), peroxidation of lipids ( p = 2.24 × 10 -5 , z-score = -1.944), Ca 2+ transport ( p = 1.55 × 10 -4 , z-score = -1.969), excitation of neurons ( p = 1.07 ×10 -4 , z-score = -1.091), and concentration of glutathione ( p = 3.06 × 10 -4 , z-score = 1.974)., Conclusion: The reduction of pro-inflammatory and oxidative stress pathways following dietary omega-3 PUFA supplementation is consistent with the promising role of these fatty acids in reducing adverse symptoms associated with neuroinflammatory diseases and painful neuropathy.

Accumulating evidence links nut consumption with an improved risk of metabolic syndrome (MetS); however, long-term trials are lacking. We examined the effects of a daily dose of walnuts for two years on MetS in a large elderly cohort. A total of 698 healthy elderly participants were randomly assigned to either a walnut supplemented or a control diet. The participants in the walnut group were provided with packaged walnuts (1, 1.5, or 2 oz. or ~15% of energy) and asked to incorporate them into their daily habitual diet. The participants in the control group were asked to continue with their habitual diet and abstain from eating walnuts and other tree nuts. Intake of n-3 fatty acid supplements was not permitted in either group. Fasting blood chemistries, blood pressure, and anthropometric measurements were obtained at baseline and at the end of intervention. A total of 625 participants (67% women, mean age 69.1 y) completed this two-year study (90% retention rate). Triglycerides decreased in both walnut (-0.94 mg/dl) and control (-0.96 mg/dl) groups, with no significant between-group differences. There was a non-significant decrease in systolic and diastolic blood pressure in the walnut group (-1.30 and -0.71 mm Hg, respectively) and no change in the control group. Fasting blood glucose decreased by ~1 point in both the walnut and control groups. There were no significant between-group differences in the development or reversion of MetS. In conclusion, supplementing the diet of older adults with a daily dose of walnuts had no effect on MetS status or any of its components, although the walnut group tended to have lower blood pressure., Competing Interests: S.R., E.R., and J.S. have received research funding through their institutions from the California Walnut Commission, Folsom, CA, USA. E.R. and J.S. are nonpaid members of the California Walnut Commission Scientific Advisory Council. E.R. was a paid member of the California Walnut Commission Health Research Advisory Group. J.S. has received honoraria from the California Walnut Commission for presentations. All other authors declare no conflict of interest.

To investigate the association between plasma concentration of vitamin B 12 and B 12 intake from supplements, fortified foods, and animal source foods among vegetarians and non-vegetarians, we conducted a cross-sectional analysis among 728 participants of the Adventist Health Study 2 (AHS-2) calibration study. The median age of participants was 58 years, 65.4% were female, and 50.3% were White. We used six 24 h dietary recalls to measure B 12 intake, serum vitamin B 12 , and holotranscobalamin (holoTC) concentration. B 12 supplements had a significantly positive association with plasma B 12 among all subjects ( p trend < 0.001), especially among vegans and lacto-ovo vegetarians ( p trend < 0.001). Among non-users of B 12 supplements, B 12 intake from milk substitutes was significantly positively associated with holoTC ( p trend < 0.004) and serum B12 ( p trend < 0.030). In non-vegetarians, holoTC was significantly positively associated with B 12 intake from eggs, while serum B 12 was significantly positively associated with B 12 intake from milk in the upper tertile compared to the lower, and B 12 intake from meat in the middle compared to the lower tertile intake ( p < 0.011). Supplements containing B 12 followed by B 12 intake from milk substitutes were significant contributors of plasma vitamin B 12 concentration., Competing Interests: The authors declare no conflict of interest.

Childhood obesity is associated with a greater chance of a lifetime of obesity. Evidence suggests dairy at recommended levels could be beneficial in maintaining normal weight and body composition. We assessed whether dairy consumption is associated with anthropometric indicators of health (z-scores for weight-for-age (WAZ); height-for-age (HAZ) and body mass index (BMIZ); waist-to-height ratio (WHtR); fat-free mass (FFM); and fat mass (FM)) in adolescents. In a cross-sectional study, 536 males and females ages 12-18 completed a 151-item semi-quantitative web-based food frequency questionnaire that included 34 dairy-containing foods. Dairy foods were categorized into milk, cheese, sweetened dairy, and total dairy. Anthropometrics were measured during school visits. Total dairy intake was associated with WAZ (β = 0.25 (95% CI: 0.01, 0.49), p = 0.045) and HAZ (β = 0.28 (95% CI: 0.04, 0.52), p = 0.021). In boys, total dairy was associated with WHtR (β = 0.02 (95% CI: 0.00, 0.04), p = 0.039), FFM (β = 4.83 (95% CI: 1.79, 7.87), p = 0.002), and FM (β = 3.89 (95% CI: 0.58, 7.21), p = 0.021), and cheese was associated with FFM (β = 4.22 (95% CI: 0.98, 7.47), p = 0.011). Dairy consumption seems to influence growth in both genders, and body composition and central obesity in boys. Prospective studies are needed to identify how types of dairy relate to growth, body composition, and central obesity of adolescents.