Differences in Metabolite Composition of Aloe barbadensis Mill. Extracts Lead to Differential Effects on Human Blood T Cell Activity In Vitro.

Aloe barbadensis Mill. (Aloe) is used for diverse therapeutic properties including immunomodulation. However, owing to the compositionally complex nature of Aloe, bioactive component(s) responsible for its beneficial properties, though thought to be attributed to polysaccharides (acemannan), remain unknown. We therefore aimed to determine the metabolite composition of various commercial Aloe extracts and assess their effects on human blood T cell activity in vitro. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in presence or absence of various Aloe extracts. T cell phenotype and proliferation were investigated by flow cytometry. Aloe extracts were analyzed using targeted 1H-NMR spectroscopy for standard phytochemical quality characterization and untargeted gas chromatography mass spectrometry (GC-MS) for metabolite profiling. Aloe extracts differing in their standard phytochemical composition had varying effects on T cell activation, proliferation, apoptosis, and cell-death in vitro, although this was not related to the acemannan content. Furthermore, each Aloe extract had its own distinct metabolite profile, where extracts rich in diverse sugar and sugar-derivatives were associated with reduced T cell activity. Our results demonstrate that all commercial Aloe extracts are unique with distinct metabolite profiles, which lead to differential effects on T cell activity in vitro, independent of the acemannan content.

The Omega-3 Fatty Acids EPA and DHA, as a Part of a Murine High-Fat Diet, Reduced Lipid Accumulation in Brown and White Adipose Tissues.

Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatory response, but the mechanisms are unclear, especially at the tissue level. Adipose tissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal white and brown adipose tissues. HFD-ED fed mice showed reduced lipid accumulation and levels of the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared with HFD-corn oil fed animals. The transcriptomic analysis showed changes in ß-oxidation pathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues.

Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials.

Background: Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. Objective: The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. Design: We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. Results: When compared with placebo, folate supplementation lowered fasting insulin (WMD: -13.47 pmol/L; 95% CI: -21.41, -5.53 pmol/L; P < 0.001) and HOMA-IR (WMD: -0.57 units; 95% CI: -0.76, -0.37 units; P < 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of >2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (ß = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (ß = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). Conclusion: Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.

Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice.

Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial ß-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.

Cereal foods are the major source of betaine in the Western diet--analysis of betaine and free choline in cereal foods and updated assessments of betaine intake.

Betaine and its precursor choline are important components of one-carbon metabolism, remethylating homocysteine into methionine and providing methyl groups for DNA methylation. Cereals are the main source of betaine in the diet, though there is little literature available on the content of betaine in cereal products, nor on betaine intake from cereals. Betaine and free-choline concentrations were measured by liquid-chromatography with tandem mass spectrometry in a wide range of commercially available cereal foods and cereal fractions. Whole grain wheat and related fractions were the best overall common source of betaine, while the pseudocereal quinoa had the highest amount of betaine measured (3900 µg/g). Based on estimates of dietary intake data cereal foods provide approximately 60-67% of betaine in Western diets, and 20-40% of betaine in South-East Asian diets. Average intake of betaine was 131 mg/d, well below those used in intervention studies using betaine to lower blood homocysteine.

Analysis of alkylresorcinols in cereal grains and products using ultrahigh-pressure liquid chromatography with fluorescence, ultraviolet, and CoulArray electrochemical detection.

Alkylresorcinols are phenolic lipids, with homologues ranging from C17 to C25, found in high concentrations in whole grain wheat and rye, lower concentrations in barley, and negligible concentrations in refined wheat flour. The analysis of alkylresorcinols is of importance due to their potential as biomarkers of whole grain intake and emerging evidence for some biological effects. Present HPLC methods have insufficient resolution for accurately quantitating the mix of alkyl- and alkenylresorcinols found in rye. An ultrahigh-pressure liquid chromatography method was developed, and three detection methods (CoulArray (CAED), ultraviolet (UV), and fluorescence detection (FD)) were compared for cereal alkylresorcinol analysis. The lower limits of quantitation and detection were 50 and 20 pg injected, 5 pg and 2 pg injected, and 500 and 1250 pg injected for FD, CAED, and UV, respectively. FD and CAED provided similar results, with some bias for higher results with FD (<10% difference). UV detection generally resulted in overestimation of alkylresorcinol concentrations. The method was applied to cereal (15) and cereal product (90) samples mainly from the United States with results in the same range as previous methods. The improved resolution with this method allows facile analysis of alkylresorcinols from cereal products, including minor unsaturated homologues such as those found in rye.