CMPF does not associate with impaired glucose metabolism in individuals with features of metabolic syndrome.

OBJECTIVE: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) is a metabolite produced endogenously from dietary sources of furan fatty acids. The richest source of furan fatty acids in human diet is fish. CMPF was recently shown to be elevated in fasting plasma in individuals with gestational diabetes and type 2 diabetes, and mechanistically high level of CMPF was linked to ß cell dysfunction. Here we aimed to study the association between plasma CMPF level and glucose metabolism in persons with impaired glucose metabolism. METHODS: Plasma CMPF concentration was measured from plasma samples of the study participants in an earlier controlled dietary intervention. All of them had impaired glucose metabolism and two other characteristics of the metabolic syndrome. Altogether 106 men and women were randomized into three groups for 12 weeks with different fish consumption (either three fatty fish meals per week, habitual fish consumption or maximum of one fish meal per week). Associations between concentration of CMPF and various glucose metabolism parameters at an oral glucose tolerance test at baseline and at the end of the study were studied. RESULTS: Fasting plasma CMPF concentration was significantly increased after a 12-week consumption of fatty fish three times per week, but the concentration remained much lower compared to concentrations reported in diabetic patients. Increases of plasma CMPF concentrations mostly due to increased fish consumption were not associated with impaired glucose metabolism in this study. Instead, elevated plasma CMPF concentration was associated with decreased 2-hour insulin concentration in OGTT. CONCLUSIONS: Moderately elevated concentration of CMPF in plasma resulting from increased intake of fish is not harmful to glucose metabolism. Further studies are needed to fully explore the role of CMPF in the pathogenesis of impaired glucose metabolism. TRIAL REGISTRATION: ClinicalTrials.gov NCT00573781.

Wild blueberries (Vaccinium myrtillus) alleviate inflammation and hypertension associated with developing obesity in mice fed with a high-fat diet.

BACKGROUND: Low-grade metabolic inflammation and hypertension are primary mechanisms involved in obesity-associated adverse health effects. Berries, especially Nordic wild blueberries (hereafter referred to as bilberries), represent an important source of dietary anthocyanins, a group of polyphenols with potential beneficial effects to combat obesity-associated metabolic disturbances. METHODS: The effects of 5% or 10% (w/w) of whole bilberries (BB) were studied on the development of obesity and its metabolic disturbances in C57BL mice fed with a high-fat diet (HFD) for three months. Cytokines, inflammatory cells, systolic blood pressure, glucose tolerance, insulin sensitivity, weight gain, body fat, food consumption and energy metabolism were assessed. RESULTS: Bilberries ameliorated type 1 pro-inflammatory responsiveness induced by HFD. This was indicated by the altered cytokine profile and the reduced prevalence of interferon gamma -producing T-cells, in particular T helper type 1 cells. Bilberries also prevented the progression of obesity associated long term increase in systolic blood pressure in mice. CONCLUSIONS: Bilberries reduce the development of systemic inflammation and prevent the progression of chronic hypertension, thus supporting their potential role in alleviating the adverse health effects associated with developing obesity.

The postprandial plasma rye fingerprint includes benzoxazinoid-derived phenylacetamide sulfates.

The bioavailability of whole-grain rye-derived phytochemicals has not yet been comprehensively characterized, and different baking and manufacturing processes can modulate the phytochemical composition of breads and other rye products. The aim of our study was to find key differences in the phytochemical profile of plasma after the consumption of 3 breads containing rye bran when compared with a plain white wheat bread control. Plasma metabolite profiles of 12 healthy middle-aged men and women were analyzed using LC quadrupole time-of-flight mass spectrometry metabolomics analysis while fasting and at 60 min, 120 min, 240 min, and 24 h after consuming a meal that contained either 100% whole-grain sourdough rye bread or white wheat bread enriched with native unprocessed rye bran or bioprocessed rye bran. White wheat bread was used as the control. The meals were served in random order after a 12-h overnight fast, with at least 3 d between each occasion. Two sulfonated phenylacetamides, hydroxy-N-(2-hydroxyphenyl) acetamide and N-(2-hydroxyphenyl) acetamide, potentially derived from the benzoxazinoid metabolites, were among the most discriminant postprandial plasma biomarkers distinguishing intake of breads containing whole-meal rye or rye bran from the control white wheat bread. Furthermore, subsequent metabolite profiling analysis of the consumed breads indicated that different bioprocessing/baking techniques involving exposure to microbial metabolism (e.g., sourdough fermentation) have a central role in modulating the phytochemical content of the whole-grain and bran-rich breads.

Effects of whole grain, fish and bilberries on serum metabolic profile and lipid transfer protein activities: a randomized trial (Sysdimet).

OBJECTIVE: We studied the combined effects of wholegrain, fish and bilberries on serum metabolic profile and lipid transfer protein activities in subjects with the metabolic syndrome. METHODS: Altogether 131 subjects (40-70 y, BMI 26-39 kg/m(2)) with impaired glucose metabolism and features of the metabolic syndrome were randomized into three groups with 12-week periods according to a parallel study design. They consumed either: a) wholegrain and low postprandial insulin response grain products, fatty fish 3 times a week, and bilberries 3 portions per day (HealthyDiet), b) wholegrain and low postprandial insulin response grain products (WGED), or c) refined wheat breads as cereal products (Control). Altogether 106 subjects completed the study. Serum metabolic profile was studied using an NMR-based platform providing information on lipoprotein subclasses and lipids as well as low-molecular-weight metabolites. RESULTS: There were no significant differences in clinical characteristics between the groups at baseline or at the end of the intervention. Mixed model analyses revealed significant changes in lipid metabolites in the HealthyDiet group during the intervention compared to the Control group. All changes reflected increased polyunsaturation in plasma fatty acids, especially in n-3 PUFAs, while n-6 and n-7 fatty acids decreased. According to tertiles of changes in fish intake, a greater increase of fish intake was associated with increased concentration of large HDL particles, larger average diameter of HDL particles, and increased concentrations of large HDL lipid components, even though total levels of HDL cholesterol remained stable. CONCLUSIONS: The results suggest that consumption of diet rich in whole grain, bilberries and especially fatty fish causes changes in HDL particles shifting their subclass distribution toward larger particles. These changes may be related to known protective functions of HDL such as reverse cholesterol transport and could partly explain the known protective effects of fish consumption against atherosclerosis. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov NCT00573781.

Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach.

SCOPE: Betaine (BET) reduces diet-induced liver lipid accumulation, and may relieve obesity-related metabolic disturbances. The aim of our study was to analyze metabolite alterations after supplementation of BET, polydextrose (PDX, a soluble dietary fiber), or their combination (BET PDX) via drinking water to C57BL/6J mice fed a high-fat (HF) diet. METHODS AND RESULTS: BET supplementation increased BET levels in plasma, muscle, and liver (p < 0.05), and the nontargeted LC-MS metabolite profiling revealed an increase in several metabolites in the carnitine biosynthesis pathway after BET supplementation both in liver and muscle. These included carnitine and acetylcarnitine (1.4-fold, p < 0.05), propionylcarnitine and γ-butyrobetaine (1.5-fold, p < 0.05), and several other short-chain acylcarnitines (p < 0.05) in muscle. These changes were slightly higher in the BET PDX group. Furthermore, BET reduced the HF diet induced accumulation of triglycerides in liver (p < 0.05). The supplementations did not attenuate the HF diet induced increase in body weight gain or the increase in adipose tissue mass. Instead, the combination of BET and PDX tended to increase adiposity. CONCLUSION: Our results suggest that increased availability of BET in different tissues, especially in muscle, after BET supplementation has an impact on carnitine metabolism, and this could further explain the link between BET and lipid metabolism.

Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study.

BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary solutions are needed to help improve glucose and lipid metabolism in persons at high risk of developing the disease. Herein we investigated the effects of low-insulin-response grain products, fatty fish, and berries on glucose metabolism and plasma lipidomic profiles in persons with impaired glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired glucose metabolism and with at least two other features of the metabolic syndrome were included in a 12-week parallel dietary intervention. The participants were randomized into three diet intervention groups: (1) whole grain and low postprandial insulin response grain products, fatty fish three times a week, and bilberries three portions per day (HealthyDiet group), (2) Whole grain enriched diet (WGED) group, which includes principally the same grain products as group (1), but with no change in fish or berry consumption, and (3) refined wheat breads (Control). Oral glucose tolerance, plasma fatty acids and lipidomic profiles were measured before and after the intervention. Self-reported compliance with the diets was good and the body weight remained constant. Within the HealthyDiet group two hour glucose concentration and area-under-the-curve for glucose decreased and plasma proportion of (n-3) long-chain PUFAs increased (False Discovery Rate p-values <0.05). Increases in eicosapentaenoic acid and docosahexaenoic acid associated curvilinearly with the improved insulin secretion and glucose disposal. Among the 364 characterized lipids, 25 changed significantly in the HealthyDiet group, including multiple triglycerides incorporating the long chain (n-3) PUFA. CONCLUSIONS/SIGNIFICANCE: The results suggest that the diet rich in whole grain and low insulin response grain products, bilberries, and fatty fish improve glucose metabolism and alter the lipidomic profile. Therefore, such a diet may have a beneficial effect in the efforts to prevent type 2 diabetes in high risk persons. TRIAL REGISTRATION: ClinicalTrials.gov NCT00573781.

Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome.

BACKGROUND: Carbohydrate modification based on rye bread and pasta enhances early insulin secretion in subjects with the metabolic syndrome. OBJECTIVE: Because the actions of insulin and cholesterol metabolism are interrelated, the question is raised of whether it is possible to alter cholesterol metabolism by means of dietary carbohydrate modification. DESIGN: We investigated the 12-wk effects of dietary carbohydrate modification on cholesterol synthesis and absorption by measuring the ratios of surrogate markers of precursor (cholestenol, desmosterol, and lathosterol) and absorption (cholestanol and plant sterols) sterols to cholesterol and their association to glucose metabolism in 74 subjects with the metabolic syndrome. The subjects were randomly assigned to diets with rye bread and pasta (RPa) or oat, wheat bread, and potato (OWPo) as the main carbohydrate source (34% and 37% of energy intake, respectively). RESULTS: During the study, serum cholesterol concentrations remained unchanged. Cholesterol synthesis was lower (6-10% for cholestenol and lathosterol; P < 0.05) and absorption higher (9%; P < 0.05 for sitosterol) with the OWPo diet than at baseline. With the RPa diet, cholesterol absorption was lower and synthesis higher than with the OWPo diet. The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r = -0.520, P < 0.05). In the combined group, the changes in the cholestanol ratio and the insulinogenic index were interrelated (r = -0.464, P < 0.001). CONCLUSIONS: Carbohydrate modifications had dissimilar effects on cholesterol metabolism. Consumption of RPa, as compared with OWPo, may be clinically more favorable because it seems to inhibit the absorption of cholesterol, a factor crucial in the development of arterial atherosclerosis.

Methodologic considerations in the measurement of glycemic index: glycemic response to rye bread, oatmeal porridge, and mashed potato.

BACKGROUND: Methodologic choices affect measures of the glycemic index (GI). The effects on GI values of blood sampling site, reference food type, and the number of repeat tests have been insufficiently determined. OBJECTIVE: The objective was to study the effect of methodologic choices on GI values. Comparisons were made between venous and capillary blood sampling and between glucose and white bread as the reference food. The number of tests needed for the reference food was assessed. Rye bread, oatmeal porridge, and instant mashed potato were used as the test foods. DESIGN: Twelve healthy volunteers were served each test food once and both reference foods 3 times at 1-wk intervals in a random order after they had fasted overnight. Capillary and venous blood samples were drawn at intervals for 3 h after each study meal. RESULTS: GIs and their CVs based on capillary samples were lower than those based on venous samples. Two tests of glucose solution as the reference provided stable capillary GIs for the test foods. The capillary GIs did not differ significantly when white bread was used as the reference 1, 2, or 3 times, but the variation was lower when tests were performed 2 and 3 times. Capillary GIs with white bread as the reference were 1.3 times as high as those with glucose as the reference. The capillary GIs of rye bread, oatmeal porridge, and mashed potato were 77, 74, and 80, respectively, with glucose as the reference. CONCLUSIONS: Capillary blood sampling should be used in the measurement of GI, and reference tests with glucose or white bread should be performed at least twice.

Determinants of aflatoxin M1 in breast milk in a selected group of Egyptian mothers.

In Egypt, there is a paucity of biomarker data on aflatoxin (AF) exposure. The study assessed the level and frequency of breast milk AFM1 as a biomarker of maternal exposure. Breast milk samples were collected from a selected group of 388 Egyptian lactating mothers of children attending the New El-Qalyub Hospital, Qalyubiyah governorate, Egypt, during May-September 2003. Following aflatoxin extraction, AFM1 levels were assessed by high-performance liquid chromatography (HPLC) with fluorescence detection. Approximately 36% of mothers tested positive for AFM1 (median 13.5 pg ml-1, interquartile range (IQR) 10.27-21.43). Non-working status (p = 0.018, odds ratio (OR) = 2.87), obesity (p = 0.004, OR = 3.01), high corn oil consumption (p = 0.002, OR = 2.21), number of children (>1) (p = 0.025, OR = 1.99), and early lactation stage (<1 month) (p = 0.028 OR = 3.57), contributed to the occurrence of AF in breast milk. AFM1 contamination of breast milk was frequent, albeit at moderate levels. Growth and development of the infant is rapid and thus it is possible that AF exposure through breast milk has a significant health effect.

Black currant seed oil and fish oil supplements differ in their effects on fatty acid profiles of plasma lipids, and concentrations of serum total and lipoprotein lipids, plasma glucose and insulin.

European diets provide a suboptimal intake of eicosapentaenoic (20:5n3) and docosahexaenoic (22:6n3) acids, which are derived mainly from fish oils. The present study indicates that black currant seed oil, which contains 14.5% alpha-linolenic (18:3n3), 12.6% gamma-linolenic (18:3n6), 47.5% linoleic (18:2n6) and 2.7% stearidonic (18:4n3) acids, could potentially serve as alternative to fish oil as a n3 fatty acid source. Fifteen healthy females participated in a randomized, double-blind, crossover study including two 4-week periods with either 3 g/day of black currant seed oil or 2.8 g/day of fish oil separated by a 4-week washout period. The results show that black currant seed oil supplementation increased the proportion of 18:3n6 in triacylglycerols (TAG) and cholesteryl esters (CE), and that of dihomo-gamma-linolenic (20:3n6) in TAGs, CEs and glycerophospholipids (GPL) (P<.05). Proportion of 18:3n6 was higher (P<.05) after black currant seed oil than after fish oil in TAGs and CEs, and that of 20:3n6 in TAGs, CEs and GPLs. Black currant seed oil supplementation caused only minor changes in the proportions of 20:5n3 or 22:6n3. Serum levels of LDL cholesterol were lower (P<.05) after black currant seed oil compared to fish oil. Plasma glucose concentration decreased during the fish oil supplementation (P<.05).

Triacylglycerol molecular weight and to a lesser extent, fatty acid positional distribution, affect chylomicron triacylglycerol composition in women.

Postprandial composition of chylomicron triacylglycerols (TAG) and their clearance may be affected by the molecular weight of TAG, their fatty acid (FA) combinations and the positional distribution of FA in TAG. Delayed postprandial TAG clearance is a risk factor for cardiovascular disease. However, due to the complexity of traditional analysis methods, the composition of individual TAG molecules is frequently overlooked. In this study, chylomicron TAG molecular weight distribution and regioisomerism were followed in 10 healthy female volunteers after two fat loads with identical FA composition but different positional distributions (palm oil and transesterified palm oil). An efficient tandem mass spectrometric method of analysis was applied. During the 6-h observation period, the relative concentrations of TAG with 48:2 [48 acyl carbons and 2 double bonds (ACN:DB)], 50:3 and 50:2 decreased, whereas the proportions of 48:0 (tripalmitin), 52:3 and 54:4 remained constant and the proportion of 54:3 (triolein) increased (P < 0.05). The existence of seven regioisomers containing palmitic, oleic and linoleic acids in different sn-positions was studied. The amount of 1,3-dipalmitoyl-2-oleoyl-sn-glycerol was less (P < 0.05) 1.5 h postprandially than at 2-5 h after palm oil, and less (P < 0.05) at 1.5 h than at 2-6 h after transesterified palm oil. This may be an indication of a loss of palmitic acid in the gut. Taken together, TAG molecular weight composition and to a lesser extent, positional distribution, seem to affect the rates of chylomicron TAG clearance in humans.