Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial.

BACKGROUND: A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss. METHODS: This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome. Patients received a specific combination of five amino acids or placebo mixed with enteral feeding for 21 days. Markers of renal function, gut barrier structure and functionality were collected at baseline and 1, 2, 3 and 8 weeks after randomization. Muscle structure and function were assessed through MRI measurements of the anterior quadriceps volume and by twitch airway pressure. Data were compared between groups relative to the baseline. RESULTS: Thirty-five critically ill patients were randomized. The amino acid blend did not impair urine output, blood creatinine levels or creatinine clearance. Plasma citrulline levels increased significantly along the treatment period in the amino acid group (difference in means [95% CI] 5.86 [1.72; 10.00] nmol/mL P = 0.007). Alanine aminotransferase and alkaline phosphatase concentrations were lower in the amino acid group than in the placebo group at one week (ratio of means 0.5 [0.29; 0.86] (P = 0.015) and 0.73 [0.57; 0.94] (P = 0.015), respectively). Twitch airway pressure and volume of the anterior quadriceps were greater in the amino acid group than in the placebo group 3 weeks after randomization (difference in means 10.6 [0.99; 20.20] cmH20 (P = 0.035) and 3.12 [0.5; 5.73] cm3/kg (P = 0.022), respectively). CONCLUSIONS: Amino acid supplementation increased plasma citrulline levels, reduced alanine aminotransferase and alkaline phosphatase levels, and improved twitch airway pressure and anterior quadriceps volume. Trial registration ClinicalTrials.gov, NCT02968836. Registered November 21, 2016.

An oleuropein-based dietary supplement may improve joint functional capacity in older people with high knee joint pain: findings from a multicentre-RCT and post hoc analysis.

OBJECTIVES: To investigate a 6-month intervention with an olive leaf extract (OLE) on knee functionality and biomarkers of bone/cartilage metabolism and inflammation. DESIGN: This randomized, double-blind, placebo-controlled, multi-centric trial included 124 subjects with knee pain or mobility issues. Subjects received twice a day one capsule of placebo or 125 mg OLE (Bonolive™, an OLE containing 50 mg of oleuropein) for 6 months. The co-primary endpoints were Knee injury and Osteoarthritis Outcome Score (KOOS) and serum Coll2-1NO2. The secondary endpoints were the subscales of the KOOS, knee pain VAS at rest and at walking, OARSI core set of performance-based tests and multiple inflammatory and bone or cartilage remodeling serum biomarkers and concentration of oleuropein's metabolites in urine. RESULTS: At 6 months, OLE group was not efficient on global KOOS score, changes of inflammatory and cartilage remodeling biomarkers compared to placebo. Post hoc analyses demonstrated a large and significant treatment effect of OLE in a sub-group of subjects with high walking pain at baseline (p = 0.03). This was observed at 6 months for the global KOOS score, and each different subscale and for pain at walking (p = 0.02). OLE treatment was well tolerated. CONCLUSION: OLE was not effective on joint discomfort excepted in a sub-group of subjects with high pain at treatment initiation. As oleuropein is well tolerated, OLE can be used to relieve knee joint pain and enhance mobility in subjects with articular pain.

Comparison of the acute metabolic effect of different infant formulas and human milk in healthy adults: a randomized trial.

BACKGROUND/OBJECTIVES: Different infant formulas, varying in protein type and quantity, are available for infants who are not breastfed or are partially breastfed. Postprandial insulinemic and glycemic responses to intact vs partially hydrolyzed protein in infant formula are unclear. To compare the effect of different forms (partially hydrolyzed vs non-hydrolyzed) and levels of protein in infant formula compared with a human milk reference subgroup on insulin response in adults. SUBJECTS/METHODS: In a randomized, double-blinded, cross-over study, 35 healthy adults consumed 600 ml of three different infant formulas: Intact protein-based formula (INTACT) (1.87 g protein/100 kcal; whey/casein ratio of 70/30; 63 kcal/100 ml), partially hydrolyzed whey-based formula (PHw) (1.96 g protein/100 kcal; 100% whey; 63 kcal/100 ml), a high-protein partially hydrolyzed whey-based formula (HPPHw) (2.79 g protein/100 kcal; 100%whey; 73 kcal/100 ml) and a subgroup also consumed human milk (HM) (n = 11). Lipid and carbohydrate (lactose) contents were similar (5.1-5.5 and 10.5-11.6 g/100 kcal, respectively). Venous blood samples were taken after overnight fasting and at different intervals for 180 min post-drink for insulin, glucose, blood lipids, GLP-1, glucagon, and C-peptide. RESULTS: Twenty-nine subjects (eight consuming HM) adhered to the protocol. INTACT and PHw groups had similar postprandial insulinemia and glycaemia (Cmax and iAUC) that were not different from those of the HM subgroup. HPPHw resulted in higher postprandial insulin responses (iAUC) relative to all other groups (p < 0.001, p < 0.001, p = 0.002 for the comparison with INTACT, PHw, HM, respectively). HPPHw resulted in a higher glucose response compared to INTACT and PHw (iAUC: p = 0.003, p = 0.001, respectively), but was not different from HM (p = 0.41). CONCLUSION: This study in adults demonstrates similar postprandial insulinemia and glycaemia between INTACT and PHw, close to that of HM, but lower than HPPHw, which had a higher protein content compared to the other test milks. The findings remain to be confirmed in infants. CLINICAL TRIAL REGISTRATION: This study is registered at clinicaltrials.gov, identifier NCT04332510.

Monoacylglycerol Form of Omega-3s Improves Its Bioavailability in Humans Compared to Other Forms.

Numerous benefits are attributed to omega-3 fatty acids (OM3) especially in cardiovascular health. However, bioavailability and clinical efficacy depend on numerous factors, including OM3 form, food matrix effects (especially the lipid content of the diet), and metabolic capacity. Here, we show in humans that a "pre-digested" OM3-sn-1(3)-monoacylglycerol lipid structure (OM3-MAG) has a significantly greater absorption at high therapeutic doses (2.9 g/day) than the most commonly OM3-ethyl ester (3.1 g/day) form (used for the treatment of hypertriglyceridemia), and a comparable profile to other pre-digested OM3 free fatty acids (OM3-FFA) structure (3.2 g/day). Nutritional supplement doses of MAG resulted in similar increases in OM3 blood level, compared to OM3 triacylglycerols (OM3-TAG) supplements in obese subjects (1.2 g/day) under low fat diet, and in children with cystic fibrosis (1.0 g/day). These results suggest that both forms of pre-digested OM3-MAG and OM3-FFA are effectively absorbed and re-incorporated effectively into triacylglycerols inside the enterocytes, before being exported into the chylomicrons lipid transport system. The pre-digested OM3-MAG might provide a more effective therapy in severe cardiovascular conditions where high doses of OM3 are required and a low-fat diet is indicated, which limited digestive lipase activity.

Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans.

The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.

The bioavailability of iron picolinate is comparable to iron sulfate when fortified into a complementary fruit yogurt: a stable iron isotope study in young women.

PURPOSE: A technological gap exists for the iron (Fe) fortification of difficult-to-fortify products, such as wet and acid food products containing polyphenols, with stable and bioavailable Fe. Fe picolinate, a novel food ingredient, was found to be stable over time in this type of matrix. The objective of this study was to measure the Fe bioavailability of Fe picolinate in a complementary fruit yogurt. METHODS: The bioavailability of Fe picolinate was determined using stable iron isotopes in a double blind, randomized cross-over design in non-anemic Swiss women (n = 19; 25.1 ± 4.6 years). Fractional Fe absorption was measured from Fe picolinate (2.5 mg 57Fe per serving in two servings given morning and afternoon) and from Fe sulfate (2.5 mg 54Fe per serving in two servings given morning and afternoon) in a fortified dairy complementary food (i.e. yogurt containing fruits). Fe absorption was determined based on erythrocyte incorporation of isotopic labels 14 days after consumption of the last test meal. RESULTS: Geometric mean (95% CI) fractional iron absorption from Fe picolinate and Fe sulfate were not significantly different: 5.2% (3.8-7.2%) and 5.3% (3.8-7.3%) (N.S.), respectively. Relative bioavailability of Fe picolinate versus Fe sulfate was 0.99 (0.85-1.15). CONCLUSION: Therefore, Fe picolinate is a promising compound for the fortification of difficult-to-fortify foods, to help meet Fe requirements of infants, young children and women of childbearing age.

Modulation of cerebral ketone metabolism following traumatic brain injury in humans.

Adaptive metabolic response to injury includes the utilization of alternative energy substrates - such as ketone bodies (KB) - to protect the brain against further damage. Here, we examined cerebral ketone metabolism in patients with traumatic brain injury (TBI; n = 34 subjects) monitored with cerebral microdialysis to measure total brain interstitial tissue KB levels (acetoacetate and ß-hydroxybutyrate). Nutrition - from fasting vs. stable nutrition state - was associated with a significant decrease of brain KB (34.7 [10th-90th percentiles 10.7-189] µmol/L vs. 13.1 [6.5-64.3] µmol/L, p < 0.001) and blood KB (668 [168.4-3824.9] vs. 129.4 [82.6-1033.8] µmol/L, p < 0.01). Blood KB correlated with brain KB (Spearman's rho 0.56, p = 0.0013). Continuous feeding with medium-chain triglycerides-enriched enteral nutrition did not increase blood KB, and provided a modest increase in blood and brain free medium chain fatty acids. Higher brain KB at the acute TBI phase correlated with age and brain lactate, pyruvate and glutamate, but not brain glucose. These novel findings suggest that nutritional ketosis was the main determinant of cerebral KB metabolism following TBI. Age and cerebral metabolic distress contributed to brain KB supporting the hypothesis that ketones might act as alternative energy substrates to glucose. Further studies testing KB supplementation after TBI are warranted.

Ingestion of a Pre-bedtime Protein Containing Beverage Prevents Overnight Induced Negative Whole Body Protein Balance in Healthy Middle-Aged Men: A Randomized Trial.

Age related muscle wasting leads to overall reductions of lean body mass, reduced muscle strength, and muscle function resulting in compromised quality of life. Utilizing novel nutritional strategies to attenuate such losses is of great importance in elderly individuals. We aimed to test if a complete dietary supplement containing 25 g of milk proteins and ingested in the evening before bed would improve protein metabolism in terms of whole body protein balance over a 10 h overnight period following ingestion of the test drink in healthy middle-aged male subjects. In addition we also assessed the rates of muscle protein synthesis during the second half of the night in order to see if previously reported extended amino acidemia during sleep results in increased rates of muscle protein synthesis. Seventeen healthy middle-aged male subjects (59.4 ± 3.2 year) consumed a dietary supplement drink at 21:00 containing either 25 g milk protein concentrate, 25 g maltodextrin, 7.75 g canola oil (treatment group), or an isocaloric protein void drink (placebo group). Muscle protein synthesis was assessed from a muscle biopsy following the continuous intravenous infusion of 13C-phenylalanine for 5 h (from 03:00 to 08:00). Whole body protein balance was greater in the treatment group (-0.13 ± 11.30 g prot/10 h) compared to placebo (-12.22 ± 6.91 g prot/10 h) (P ≤ 0.01). In contrast, no changes were observed on rates of muscle protein synthesis during the second half of the night. Ingestion of a dietary supplement containing 25 g of milk proteins significantly reduced the negative protein balance observed during the night. Therefore, pre-bedtime protein ingestion may attenuate overnight losses of lean tissue in healthy elderly men. Despite increases in aminoacidemia during the second part of the night, no changes were observed in the rates of muscle protein synthesis during this time. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02041143.

Vegan and Animal Meal Composition and Timing Influence Glucose and Lipid Related Postprandial Metabolic Profiles.

SCOPE: Flexitarian dieting is increasingly associated with health benefits. The study of postprandial metabolic response to vegan and animal diets is essential to decipher how specific diet components may mediate metabolic changes. METHODS AND RESULTS: A randomized, crossover, controlled vegan versus animal diet challenge is conducted on 21 healthy participants. Postprandial metabolic measurements are conducted at seven timepoints. Area under the curve analysis of the vegan diet response demonstrates higher glucose (EE 0.35), insulin (EE 0.38), triglycerides (EE 0.72), and nine amino acids at breakfast (EE 4.72-209.32); and six lower health-promoting fatty acids at lunch (EE -0.1035 to -0.13) (p < 0.05). CONCLUSIONS: Glycemic and lipid parameters vary irrespective of diet type, demonstrating that vegan and animal meals contain health-promoting and suboptimal nutrient combinations. The vegan breakfast produces the same pattern of elevated branched chain amino acids, insulin, and glucose as the animal diet from the fasting results, reflecting the low protein load in the animal and the higher branched-chain amino acid load of the vegan breakfast. Liberalization of the vegan menu to vegetarian and the animal menu to a Nordic-based diet can result in optimal metabolic signatures for both flexitarian diet strategies in future research.

Effects of protein quantity and type on diet induced thermogenesis in overweight adults: A randomized controlled trial.

BACKGROUND & AIMS: Protein content of a meal is hypothesized to drive DIT dose-dependently. However, no single meal study exists comparing two different doses of protein on DIT. In addition, the source of protein, particularly whey protein, was shown to have a higher DIT than casein and soy in the acute setting, however the mechanism behind this difference is not yet clear. The aim of the present work is therefore to evaluate the efficacy of two different doses and types of protein (whey protein and casein) on DIT in overweight adults. METHODS: Randomized, double blind crossover including seventeen overweight men and women assigned to four isocaloric study treatments where protein and carbohydrate were exchanged: control, 30 g of whey protein microgels (WPM30), 50 g WPM (WPM50) or 50 g micellar casein (MC50). Energy expenditure was measured by indirect calorimetry. Blood, breath and urine samples were collected in order to measure substrate oxidation, amino acid profile, glucose and insulin, protein turnover and other metabolic parameters. RESULTS: DIT was 6.7 ± 3.7%, 13.0 ± 5.0%, 18.0 ± 5.0% and 16.0 ± 5.0% for control, WPM30, WPM50 and MC50, respectively. There was a significant difference between WPM50 and WPM30 (p < 0.005) and a trend was observed between WPM50 and MC50 (p = 0.06). WPM50 resulted in the highest total, essential, and branched-chain plasma amino acid concentrations when compared with the other study treatments (p < 0.005) and a higher insulin concentration than MC50 (p < 0.005). Protein oxidation was higher for WPM50 than MC50. Protein turnover was significantly correlated with DIT through total leucine oxidation (r = 0.52, p = 0.005). CONCLUSIONS: Our findings show that DIT does increase at a dose beyond 30 g of WPM and that the type of dairy protein may have an effect on DIT with WPM tending towards a higher DIT than casein. Although further research is required to understand the mechanism behind the effect of different protein sources on thermogenesis, we suggest that amongst the components of protein turnover, protein oxidation may be an important driver of thermogenesis at doses higher than 30 g. These results have concrete implications when choosing a dose of protein to optimize its thermogenic effect. CLINICAL TRIAL REGISTRY NUMBER: NCT02303080 www.clinicaltrials.gov.

Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and Amino Acid Metabolism in Healthy People.

SCOPE: The objective of this study is to develop a new methodology to identify the relationship between dietary patterns and metabolites indicative of food intake and metabolism. METHODS AND RESULTS: Plasma and urine samples from healthy Swiss subjects (n = 89) collected over two time points are analyzed for a panel of host-microbial metabolites using GC- and LC-MS. Dietary intake is evaluated using a validated food frequency questionnaire. Dietary pattern clusters and relationships with metabolites are determined using Non-Negative Matrix Factorization (NNMF) and Sparse Generalized Canonical Correlation Analysis (SGCCA). Use of NNMF allows detection of latent diet clusters in this population, which describes a high intake of meat or vegetables. SGCCA associates these clusters to i) diet-host microbial and lipid associated bile acid metabolism, and ii) essential amino acid metabolism. CONCLUSION: This novel application of NNMF and SGCCA allows detection of distinct metabotypes for meat and vegetable dietary patterns in a heterogeneous population. As many of the metabolites associated with meat or vegetable intake are the result of host-microbiota interactions, the findings support a role for microbiota mediating the metabolic imprinting of different dietary choices.

Short-Term Daily Intake of Polydextrose Fiber Does Not Shorten Intestinal Transit Time in Constipated Adults: A Randomized Controlled Trial.

Chronic constipation (CC) remains a common gastrointestinal (GI) disorder that conveys a substantial healthcare burden. Expert guidelines recommend increasing fiber intake, yet the clinical evidence to support this needs strengthening for specific fibers. The aim was to evaluate changes in intestinal transit time and GI symptoms in CC patients who consumed polydextrose. In a randomized, double-blind, placebo-controlled trial, 128 adults with CC received 8 g or 12 g polydextrose, or placebo, daily for 4 weeks. Transit time, as primary outcome, was assessed by radiopaque marker distribution after 2-weeks intervention. Bowel habits, GI symptoms and quality of life (QOL) were assessed by questionnaire, including the Patient-Assessment of Constipation (PAC) Symptoms (SYM), and PAC-QOL. Following 2-weeks intervention, no reduction was seen in transit time in any group and following 2- or 4-weeks intervention, no improvements were seen in stool frequency or consistency in any group. After 2-weeks intervention with 8 g/day polydextrose an improvement was seen in the PAC-SYM rectal score (p = 0.041). After 4-weeks intervention both rectal (p = 0.049) and stool (p = 0.029) scores improved while improvement in the QOL satisfaction score did not reach significance (p = 0.071). Overall, the results suggest that 2-weeks consumption of 8 or 12 g/day polydextrose does not significantly improve physiological measures of gut function in CC adults. Longer term consumption may improve clinical measures, but further studies will be required to substantiate this.

Nutritional Ketosis Increases NAD+/NADH Ratio in Healthy Human Brain: An in Vivo Study by 31P-MRS.

Ketones represent an important alternative fuel for the brain under glucose hypo-metabolic conditions induced by neurological diseases or aging, however their metabolic consequences in healthy brain remain unclear. Here we report that ketones can increase the redox NAD+/NADH ratio in the resting brain of healthy young adults. As NAD is an important energetic and signaling metabolic modulator, these results provide mechanistic clues on how nutritional ketosis might contribute to the preservation of brain health.

A 48-Hour Vegan Diet Challenge in Healthy Women and Men Induces a BRANCH-Chain Amino Acid Related, Health Associated, Metabolic Signature.

SCOPE: Research is limited on diet challenges to improve health. A short-term, vegan protein diet regimen nutritionally balanced in macronutrient composition compared to an omnivorous diet is hypothesized to improve metabolic measurements of blood sugar regulation, blood lipids, and amino acid metabolism. METHODS AND RESULTS: This randomized, cross-over, controlled vegan versus animal diet challenge is conducted on 21 (11 female,10 male) healthy participants. Fasting plasma is measured during a 3 d diet intervention for clinical biochemistry and metabonomics. Intervention diet plans meet individual caloric needs. Meals are provided and supervised. Diet compliance is monitored. CONCLUSIONS: The vegan diet lowers triglycerides, insulin and homeostatic model assessment (HOMA-IR), bile acids, elevated magnesium levels, and changed branched-chain amino acids (BCAAs) metabolism (p < 0.05), potentiating insulin and blood sugar control after 48 h. Cholesterol control improves significantly in the vegan versus omnivorous diets. Plasma amino acid and magnesium concentrations positively correlate with dietary amino acids. Polyunsaturated fatty acids and dietary fiber inversely correlate with insulin, HOMA-IR, and triglycerides. Nutritional biochemistries, BCAAs, insulin, and HOMA-IR are impacted by sexual dimorphism. A health-promoting, BCAA-associated metabolic signature is produced from a short-term, healthy, controlled, vegan diet challenge when compared with a healthy, controlled, omnivorous diet.

Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects.

Caffeine induces positive effects on sustained attention, although studies assessing the acute effects of low caffeine dose (<75 mg) on sustained attention are limited and use short-term tests. Therefore, we investigated the acute effects of a 60 mg dose of caffeine on sustained attention in tests lasting up to 45 minutes using 82 low or non-caffeine-consuming healthy male ( n=41) and female ( n=41) adults aged between 40 and 60 years. Vigilance was measured using Mackworth Clock test, Rapid Visual Information Processing Test, adaptive tracking test, saccadic eye movement and attention switch test. Effects on mood and fatigue were analysed using Bond and Lader and Caffeine Research visual analogue scales, and Samn-Perelli questionnaire. Saliva sampling was performed for both compliance and caffeine pharmacokinetic analysis. Administration of a 60 mg caffeine dose resulted in a significant improvement in sustained attention compared with the placebo. Also a significantly improved peak saccadic velocity and reaction time performance was found, and decreased error rate. Significantly increased feelings of alertness, contentment and overall mood after caffeine treatment compared with placebo were observed. This study demonstrated that in healthy adult subjects oral administration of a single 60 mg caffeine dose elicited a clear enhancement of sustained attention and alertness, measured both in multiple objective performances and in subjective scales.

Effects of TRP channel agonist ingestion on metabolism and autonomic nervous system in a randomized clinical trial of healthy subjects.

Various lines of published evidence have already demonstrated the impact of TRPV1 agonists on energetic metabolism through the stimulation of the sympathetic nervous system (SNS). This study presents a trial investigating if stimulation of the two related sensory receptors TRPA1 and TRPM8 could also stimulate the SNS and impact the energetic metabolism of healthy subjects. The trial was designed to be double-blinded, randomized, cross-over, placebo-controlled with healthy subjects and the impact on the energetic metabolism and the autonomic nervous system (ANS) of cinnamaldehyde, capsaicin and a cooling flavor was measured during the 90 min after ingestion. Energy expenditure and substrate oxidation were measured by indirect calorimetry. An exploratory method to measure ANS activity was by facial thermography and power spectral analysis of heart rate variability using ECG was also used. Following cinnamaldehyde ingestion, energy expenditure was increased as compared to placebo. Furthermore, postprandial fat oxidation was maintained higher compared to placebo after cinnamaldehyde and capsaicin ingestion. Similar peripheral thermoregulation was observed after capsaicin and cinnamaldehyde ingestion. Unlike capsaicin, the dose of cinnamaldehyde was not judged to be sensorially 'too intense' by participants suggesting that Cinnamaldehyde would be a more tolerable solution to improve thermogenesis via spicy ingredients as compared to capsaicin.

The roasting process does not influence the extent of conjugation of coffee chlorogenic and phenolic acids.

Understanding the bioavailability and metabolism of coffee compounds will contribute to identify the unknown biological mechanism(s) linked to their beneficial effects. The influence of the roasting process on the metabolism of coffee chlorogenic acids in humans was evaluated. In a randomized, double-blind, crossover study, 12 healthy volunteers consumed four instant coffees namely, high roasted coffee (HRC), low roasted coffee (LRC), unroasted coffee (URC), and in vitro hydrolyzed unroasted coffee (HURC). The sum of areas under the curve (AUC) ranged from 8.65-17.6 to 30.9-126 µM/h (P < 0.05) for HRC, LRC, URC, and HURC, respectively. The AUC of HRC, LRC, and URC was correlated with the initial level of phenolic acids in the coffee drinks. Despite different absorption rates, the extent of conjugation was comparable between HRC, LRC, and URC coffees but different for HURC. The most abundant circulating metabolites during the first 5 H were dihydroferulic acid (DHFA), caffeic acid-3'-O-sulfate (CA3S) and isoferulic-3'-O-glucuronide (iFA3G). DHFA and 5-4-dihydro-m-coumaric acid (mDHCoA) were the main metabolites in the period of 5-24 H. The phenolic compounds after consumption of HURC were most rapidly absorbed (Tmax 1 H) compared with the other coffees (Tmax between 9 and 11 H). Using coffees with different degrees of roasting we highlighted that in spite of different absorption rates the extent of conjugation of phenolic acids was comparable. In addition, by using a hydrolyzed unroasted coffee we demonstrated an increased absorption of phenolic acids in the small intestine. © 2016 BioFactors, 42(3):259-267, 2016.

Vitamin E and vitamin E acetate absorption from self-assembly systems under pancreas insufficiency conditions.

We determined the bioavailability of vitamin E from self-assembly structures in patients with diagnosed chronic pancreas insufficiency. Vitamin E solubilized in dispersed inverted bicontinuous cubic phase and in micellar formulation was delivered directly to the small intestine by tube-feeding. A cross-over study with randomization of 6 subjects and 2 treatments including a combined dose of 18 mg (27 IU) of vitamin E (RRR-[5,7-methyl-((2)H6)]-α-tocopherol) and 27 mg (27 IU) vitamin E acetate (RRR-[5-methyl-(2)H3]-α-tocopheryl acetate) was applied over a time period of 1 h. Plasma samples were collected for 56 h and analyzed by liquid chromatography-mass spectrometry. Appearance of labeled tocopherols originating from the treatment started at 25 h and reached Cmax (0.6-4.6 µM depending on subject) in the 7-9 h window. From the Tmax onwards, both forms of tocopherols diminished slowly to 30-50% of their maxima within 56 h. Strong inter-individual variation was observed in the plasma appearance curves (relative standard deviation varied between 38-45%). No significant discrimination was found between the absorption of free or acetylated forms of deuterated α-tocopherol confirming that application of acetylated α-tocopherol provides the same bioavailability as free α-tocopherol. This observation is valid in both dispersed inverted bicontinuous cubic phase and micellar formulations. Furthermore, since the area-under-the-curve values from cubic phase and from micellar formulations are similar, the cubic phase formulation could represent an alternative delivery system for lipophilic micronutrients in conditions or studies where polysorbate-based micelles cannot be generated.

Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.

SCOPE: Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. OBJECTIVE AND STUDY DESIGN: We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. RESULTS: CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. CONCLUSION: This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses.