Feeding of fish oil and medium-chain triglycerides to canines impacts circulating structural and energetic lipids, endocannabinoids, and non-lipid metabolite profiles.

Introduction: The effect of medium-chain fatty acid-containing triglycerides (MCT), long-chain polyunsaturated fatty acid-containing triglycerides from fish oil (FO), and their combination (FO+MCT) on the serum metabolome of dogs (Canis familiaris) was evaluated. Methods: Dogs (N = 64) were randomized to either a control food, one with 7% MCT, one with FO (0.18% eicosapentaenoate and 1.3% docosahexaenoate), or one with FO+MCT for 28 days following a 14-day washout period on the control food. Serum metabolites were analyzed via chromatography followed by mass spectrometry. Results: Additive effects of serum metabolites were observed for a number of metabolite classes, including fatty acids, phospholipids, acylated amines including endocannabinoids, alpha-oxidized fatty acids, and methyl donors. Some effects of the addition of FO+MCT were different when the oils were combined compared with when each oil was fed separately, namely for acylcarnitines, omega-oxidized dicarboxylic acids, and amino acids. Several potentially beneficial effects on health were observed, including decreased circulating triglycerides and total cholesterol with the addition of FO (with or without MCT) and decreases in N-acyl taurines with the addition of MCT, FO, or FO+MCT. Discussion: Overall, the results of this study provide a phenotypic characterization of the serum lipidomic response to dietary supplementation of long-chain n3-polyunsaturated and medium-chain saturated fats in canines.

Dietary Betaine and Fatty Acids Change Circulating Single-Carbon Metabolites and Fatty Acids in the Dog.

In order to evaluate the interaction of betaine and n-3 PUFA in foods consumed by the dog, six extruded dry foods were formulated. The control food had no specific source of added betaine or n-3 fatty acids, while the test foods were supplemented with betaine, flax or fish oil in a 2 × 3 factorial design (no added n-3 source, added flax, added menhaden fish oil, and all with or without added betaine). Forty eight adult dogs were used in this study. All dogs were assigned to one of the six dietary treatments and consumed that food for the length of the 60-day study. Blood was analyzed for metabolomics (plasma), fatty acids and selected health-related analytes (serum) at the beginning and the end of the study. Added dietary betaine increased single-carbon metabolites (betaine, dimethyl glycine, methionine and N-methylalanine), decreased xenobiotics (stachydrine, N-acetyl-S-allyl-L-cysteine, 4-vinylguaiacol sulfate, pyrraline, 3-indoleglyoxylic acid, N-methylpipecolate and ectoine) and enhanced the production of eicosapentaenoic acid (EPA). Dietary betaine also decreased the concentration of circulating carnitine and a number of carnitine-containing moieties. The addition of the n-3 fatty acids alpha-linolenic, EPA and docosahexaenoic acid (DHA) increased their respective circulating concentrations as well as those of many subsequent moieties containing these fatty acids. The addition of alpha-linolenic acid increased the concentration of EPA when expressed as a ratio of EPA consumed.

Dietary Fatty Acids Change Circulating Fatty Acids, Microbial Putrefactive Postbiotics and Betaine Status in the Cat.

There is a normal variation of polyunsaturated fatty acids (PUFA) in the foods consumed both by the domestic cat and wild felines. This variation may lead to specific changes in metabolites and circulating fatty acids that influence health and response to disease. Therefore, in order to evaluate the response to these changes in dietary PUFA three foods were formulated: a complete and balanced control food (COF) with no enhanced source of added PUFA (ARA = 0.08%, EPA & DHA = 0.01%), Test food 1 (E&DF) like the COF with added eicosapentaenoic acid EPA and docosahexaenoic acid DHA (E&D = 0.36%)) from menhaden fish oil, and Test Food 2 (ARAF) like the COF with added arachidonic acid (ARA = 0.16%) from liver. All test foods had similar protein concentrations and similar vitamin and mineral concentrations while the PUFA supplemented foods had slightly higher fat concentrations. Cats (n = 36) were fed a pre-trial food for 28 days and then assigned to a group fed either the control, E&DF or ARAF for 56 days (12 cats per group). Blood samples were drawn and serum analyzed for fatty acids, albumin, urea, creatinine, cholesterol and triglycerides at the beginning of the study and after consuming the test foods for 28 and 56 days. Plasma was similarly analyzed for metabolomics. Increasing dietary E&D resulted in reduced cholesterol, betaine, dimethyl glycine, sarcosine and 4-ethylphenylsulfate. Increasing dietary ARA resulted in reduced betaine, dimethyl glycine and sarcosine and an increased concentration of indoleacetate, indolepropionate and indoleacetylglutamine. These data suggest a benefit of dietary single carbon metabolism support for cats supplemented with ARA or E&D. Moreover, the reduction in circulating cholesterol and triglycerides through dietary E&D supplementation could benefit cats with hyperlipidemia. Further research into the interrelationship between dietary PUFA and the gut microbe will benefit from the data showing that ARA increased specific positive postbiotics (i.e., indoleacetate, indolepropionate) while E&D supplementation showed the benefit of reducing some postbiotics which have been associated with reduced health (4-ethylphenylsulfate, 3-methyl catechol sulfate and 4-vinylphenol sulfate).

Resistant starch analysis of commonly consumed potatoes: Content varies by cooking method and service temperature but not by variety.

Resistant starch (RS) has unique digestive and absorptive properties which may provide health benefits. We conducted a study to determine the contributions of cultivar, cooking method and service temperature on the RS contents of potatoes (Solanum tuberosum L.). We hypothesized that the RS content would vary by variety, cooking method and service temperature. Potatoes of three common commercial varieties (Yukon Gold, Dark Red Norland, and Russet Burbank) were subjected to two methods of cooking (baking or boiling) and three service temperatures: hot (65°C), chilled (4°C) and reheated (4°C for 6d; reheated to 65°C) and analyzed the starch content by modification of a commercially available assay. Results showed that RS content (g/100g) varied by cooking method and service temperature but not variety. Baked potatoes had higher RS contents than boiled; chilled potatoes had more RS than either hot or reheated. These results may assist in dietary choices for reducing chronic disease risk.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in cats.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lysine, leucine, and fiber on weight loss and maintenance in cats. DESIGN: Prospective clinical study. ANIMALS: 50 overweight cats. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 cats were allocated to 3 groups (10 cats/group) to be fed a dry maintenance cat food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 cats was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1%/wk (weight loss phase). Next, each cat was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Cats were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, cats in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, cats lost a significant amount of body weight and fat mass but retained lean body mass during the weight loss phase and continued to lose body weight and fat mass but gained lean body mass during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism was improved from baseline for cats fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight cats the test food caused weight loss and improvements in body condition during the weight maintenance phase, possibly because the food composition improved energy metabolism.

Effect of feeding a weight loss food beyond a caloric restriction period on body composition and resistance to weight gain in dogs.

OBJECTIVE: To determine the effect of feeding a food with coconut oil and supplemental L-carnitine, lipoic acid, lysine, leucine, and fiber on weight loss and maintenance in dogs. DESIGN: Prospective clinical study. ANIMALS: 50 overweight dogs. PROCEDURES: The study consisted of 2 trials. During trial 1, 30 dogs were allocated to 3 groups (10 dogs/group) to be fed a dry maintenance dog food to maintain body weight (group 1) or a dry test food at the same amount on a mass (group 2) or energy (group 3) basis as group 1. During trial 2, each of 20 dogs was fed the test food and caloric intake was adjusted to maintain a weight loss rate of 1% to 2%/wk (weight loss phase). Next, each dog was fed the test food in an amount calculated to maintain the body weight achieved at the end of the weight loss phase (weight maintenance phase). Dogs were weighed and underwent dual-energy x-ray absorptiometry monthly. Metabolomic data were determined before (baseline) and after each phase. RESULTS: During trial 1, dogs in groups 2 and 3 lost significantly more weight than did those in group 1. During trial 2, dogs lost a significant amount of body weight and fat mass but retained lean body mass (LBM) during the weight loss phase and continued to lose body fat but gained LBM during the weight maintenance phase. Evaluation of metabolomic data suggested that fat metabolism and LBM retention were improved from baseline for dogs fed the test food. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that feeding overweight dogs the test food caused weight loss and improvements in body condition during the weight-maintenance phase, possibly because the food composition improved energy metabolism.

Metabolism of selenite to selenosugar and trimethylselenonium in vivo: tissue dependency and requirement for S-adenosylmethionine-dependent methylation.

Impaired S-adenosylmethionine (SAM)-dependent transmethylation and methylation capacity feature in diseases related to obesity or aging, and selenium (Se) metabolism is altered in these states. We tested the hypothesis that SAM metabolism is required for methylation and excretion of Se in a rat model. Four hours after selenite and periodate-oxidized adenosine (POA; an inhibitor of SAM metabolism) were administered, circulating markers of single-carbon status were unchanged, except for decreased circulating phosphatidylcholine (P<.05). In contrast, liver and kidney SAM and S-adenosylhomocysteine were elevated (P<.05 for all). Concentrations of total Se were significantly elevated in both liver (P<.001) and kidney (P<.01), however the degree of accumulation in liver was significantly greater than that of kidney (P<.05). Red blood cell Se levels were decreased (P=.01). Trimethylselenonium levels were decreased in liver and kidney (P=.001 for both tissues) and Se-methyl-N-acetylselenohexosamine selenosugar was decreased in liver (P=.001). Urinary output of both trimethylselenonium (P=.001) and selenosugar (P=.01) was decreased as well. Trimethylselenonium production is more inhibited by POA than is selenosugar production (P<.05). This work indicates that low molecular weight Se metabolism requires SAM-dependent methylation, and disrupting the conversion of SAM to S-adenosylhomocysteine prevents conversion of selenite and intermediate metabolites to final excretory forms, suggesting implications for selenium supplementation under conditions where transmethylation is suboptimal, such as in the case of obese or aging individuals.

Differential responses to selenomethionine supplementation by sex and genotype in healthy adults.

A year-long intervention trial was conducted to characterise the responses of multiple biomarkers of Se status in healthy American adults to supplemental selenomethionine (SeMet) and to identify factors affecting those responses. A total of 261 men and women were randomised to four doses of Se (0, 50, 100 or 200 µg/d as L-SeMet) for 12 months. Responses of several biomarkers of Se status (plasma Se, serum selenoprotein P (SEPP1), plasma glutathione peroxidase activity (GPX3), buccal cell Se, urinary Se) were determined relative to genotype of four selenoproteins (GPX1, GPX3, SEPP1, selenoprotein 15), dietary Se intake and parameters of single-carbon metabolism. Results showed that supplemental SeMet did not affect GPX3 activity or SEPP1 concentration, but produced significant, dose-dependent increases in the Se contents of plasma, urine and buccal cells, each of which plateaued by 9-12 months and was linearly related to effective Se dose (µg/d per kg0·75). The increase in urinary Se excretion was greater for women than men, and for individuals of the GPX1 679 T/T genotype than for those of the GPX1 679 C/C genotype. It is concluded that the most responsive Se-biomarkers in this non-deficient cohort were those related to body Se pools: plasma, buccal cell and urinary Se concentrations. Changes in plasma Se resulted from increases in its non-specific component and were affected by both sex and GPX1 genotype. In a cohort of relatively high Se status, the Se intake (as SeMet) required to support plasma Se concentration at a target level (Se(pl-target)) is: Se(in) = [(Se(pl - target) - Se(pl))/(18.2ng d kg°.75/ml per mu g)] .

Determinants of selenium status in healthy adults.

BACKGROUND: Selenium (Se) status in non-deficient subjects is typically assessed by the Se contents of plasma/serum. That pool comprises two functional, specific selenoprotein components and at least one non-functional, non-specific components which respond differently to changes in Se intake. A more informative means of characterizing Se status in non-deficient individuals is needed. METHODS: Multiple biomarkers of Se status (plasma Se, serum selenoprotein P [SEPP1], plasma glutathione peroxidase activity [GPX3], buccal cell Se, urinary Se) were evaluated in relation to selenoprotein genotypes (GPX1, GPX3, SEPP1, SEP15), dietary Se intake, and parameters of single-carbon metabolism in a cohort of healthy, non-Se-deficient men (n = 106) and women (n = 155). CONCLUSIONS: Plasma Se concentration was 142.0 ± 23.5 ng/ml, with GPX3 and serum-derived SEPP1 calculated to comprise 20% and 34%, respectively, of that total. The balance, comprised of non-specific components, accounted for virtually all of the interindividual variation in total plasma Se. Buccal cell Se was associated with age and plasma homocysteine (hCys), but not plasma Se. SEPP1 showed a quadratic relationship with body mass index, peaking at BMI 25-30. Urinary Se was greater in women than men, and was associated with metabolic body weight (kg0.75), plasma folate, vitamin B12 and hCys (negatively). One GPX1 genotype (679T/T) was associated with significantly lower plasma Se levels than other allelic variants. Selenium intake, estimated from food frequency questionnaires, did not predict Se status as indicated by any biomarker. These results show that genotype, methyl-group status and BMI contribute to variation in Se biomarkers in Se-adequate individuals.

Surveying selenium speciation from soil to cell--forms and transformations.

The aim of this review is to present and evaluate the present knowledge of which selenium species are available to the general population in the form of food and common supplements and how these species are metabolized in mammals. The overview of the selenium sources takes a horizontal approach, which encompasses identification of new metabolites in yeast and food of plant and animal origin, whereas the survey of the mammalian metabolism takes a horizontal as well as a vertical approach. The vertical approach encompasses studies on dynamic conversions of selenium compounds within cells, tissues or whole organisms. New and improved sample preparation, separation and detection methods are evaluated from an analytical chemical perspective to cover the progress in horizontal speciation, whereas the analytical methods for the vertical speciation and the interpretations of the results are evaluated from a biological angle as well.

Chemical form of selenium affects its uptake, transport, and glutathione peroxidase activity in the human intestinal Caco-2 cell model.

Determining the effect of selenium (Se) chemical form on uptake, transport, and glutathione peroxidase activity in human intestinal cells is critical to assess Se bioavailability at nutritional doses. In this study, we found that two sources of L-selenomethionine (SeMet) and Se-enriched yeast each increased intracellular Se content more effectively than selenite or methylselenocysteine (SeMSC) in the human intestinal Caco-2 cell model. Interestingly, SeMSC, SeMet, and digested Se-enriched yeast were transported at comparable efficacy from the apical to basolateral sides, each being about 3-fold that of selenite. In addition, these forms of Se, whether before or after traversing from apical side to basolateral side, did not change the potential to support glutathione peroxidase (GPx) activity. Although selenoprotein P has been postulated to be a key Se transport protein, its intracellular expression did not differ when selenite, SeMSC, SeMet, or digested Se-enriched yeast was added to serum-contained media. Taken together, our data show, for the first time, that the chemical form of Se at nutritional doses can affect the absorptive (apical to basolateral side) efficacy and retention of Se by intestinal cells; but that, these effects are not directly correlated to the potential to support GPx activity.

Selenium and anticarcinogenesis: underlying mechanisms.

PURPOSE OF REVIEW: To discuss recent research related to anticarcinogenic mechanisms of selenium action in light of the underlying chemical/biochemical functions of the selenium species, likely to be executors of those effects. RECENT FINDINGS: Recent studies in a variety of model systems have increased the understanding of the anticarcinogenic mechanisms of selenium compounds. These include effects on gene expression, DNA damage and repair, signaling pathways, regulation of cell cycle and apoptosis, metastasis and angiogenesis. These effects would appear to be related to the production of reactive oxygen species produced by the redox cycling, modification of protein-thiols and methionine mimicry. Three principle selenium metabolites appear to execute these effects: hydrogen selenide, methylselenol and selenomethionine. The fact that various selenium compounds can be metabolized to one or more of these species but differ in anticarcinogenic activity indicates competing pathways of their metabolic and chemical/biochemical disposition. Increasing knowledge of selenoprotein polymorphisms has shown that at least some are related to cancer risk and may affect carcinogenesis indirectly by influencing selenium metabolism. SUMMARY: The anticarcinogenic effects of selenium compounds constitute intermediate mechanisms with several underlying chemical/biochemical mechanisms such as redox cycling, alteration of protein-thiol redox status and methionine mimicry.