Effects of γ-aminobutyric acid supplementation on glucose control in adults with prediabetes: A double-blind, randomized, placebo-controlled trial.

BACKGROUND: Gamma-aminobutyric acid (GABA) is mainly known as an endogenously produced neurotransmitter. However, GABA intake from dietary sources like tomatoes and fermented foods can be considerable. Studies in rodent models have shown beneficial effects of oral GABA supplementation on glucose homeostasis and cardiovascular health. Still, it is currently unknown whether oral GABA supplementation produces cardiometabolic benefits in humans. OBJECTIVES: This study aimed to investigate whether oral GABA supplementation can improve glucose homeostasis in individuals at risk of developing type 2 diabetes. METHODS: In a randomized, placebo-controlled, double-blind, parallel-arm trial, 52 individuals with prediabetes (classified by impaired glucose tolerance and/or impaired fasting glucose), aged 50 to 70 y with a body mass index ≥25 kg/m2 received either 500 mg GABA 3 times daily or a placebo for 95 days. The primary outcome was the effect of the intervention on glucose response after an OGTT. As exploratory secondary outcomes, markers of glycemic control (glycated hemoglobin, insulin, glucagon, mean amplitude of glycemic excursions, and standard deviation as measured with flash glucose monitoring), cardiovascular health (blood pressure, 24-h blood pressure, circulating triglycerides, cholesterol), and self-reported sleep quality were measured before and after the intervention. RESULTS: Compared with placebo, GABA supplementation for 95 days did not change the postprandial glucose response (0.21 mmol/L; 95% confidence interval: -0.252, 0.674; P = 0.364). After correction for the false discovery rate, all other outcomes (including fasting plasma GABA concentration) showed no significant effects from GABA intervention at a group level. CONCLUSIONS: GABA supplementation does not change the postprandial glucose response in individuals at risk of developing type 2 diabetes. However, based on findings in secondary outcome measures, further research is warranted in other study populations. Research could focus on the effects of GABA in individuals with advanced diabetes or other cardiometabolic disorders. This trial was registered at www. CLINICALTRIALS: gov as NCT04303468.

The influence of a tomato food matrix on the bioavailability and plasma kinetics of oral gamma-aminobutyric acid (GABA) and its precursor glutamate in healthy men.

Gamma-aminobutyric acid (GABA) and its precursor glutamate play signaling roles in a range of tissues. Both function as neurotransmitters in the central nervous system, but they also modulate pancreatic and immune functioning, for example. Besides endogenous production, both compounds are found in food products, reaching relatively high levels in tomatoes. Recent studies in rodents suggest beneficial effects of oral GABA on glucose homeostasis and blood pressure. However, the bioavailability from food remains unknown. We studied the bioavailability of GABA and glutamate from tomatoes relative to a solution in water. After a fasting blood sample was taken, eleven healthy men randomly received 1 liter of 4 different drinks in a cross-over design with a one-week interval. The drinks were a solution of 888 mg L-1 GABA, a solution of 3673 mg L-1 glutamate, pureed fresh tomatoes and plain water as the control. Following intake, 18 blood samples were taken at intervals for 24 hours. Plasma GABA and glutamate concentrations were determined by ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Fasting plasma GABA and glutamate concentrations were found to be 16.71 (SD 2.18) ng mL-1 and 4626 (SD 1666) ng mL-1, respectively. Fasting GABA levels were constant (5.8 CV%) between individuals, while fasting glutamate levels varied considerably (23.5 CV%). GABA from pureed tomatoes showed similar bioavailability to that of a solution in water. For glutamate, the absorption from pureed tomatoes occurred more slowly as seen from a longer tmax (0.98 ± 0.14 h vs. 0.41 ± 0.04 h, P = 0.003) and lower Cmax (7815 ± 627 ng mL-1vs. 16 420 ± 2778 ng mL-1, P = 0.006). These data suggest that GABA is bioavailable from tomatoes, and that food products containing GABA could potentially induce health effects similar to those claimed for GABA supplements. The results merit further studies on the bioavailability of GABA from other food products and the health effects of GABA-rich diets. The clinical trial registry number is NCT04086108 (https://clinicaltrials.gov/ct2/show/NCT04303468).

DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial.

PURPOSE: Trials aiming to lower homocysteine by B-vitamin supplementation have reported mixed results on slowing cognitive decline. We investigated if efficacy of B-vitamin supplementation is affected by baseline plasma omega-3 fatty acid levels. METHODS: This post-hoc analysis of the B-proof trial included 191 adults aged 65 years or older with baseline plasma total homocysteine ≥ 12 µmol/L, randomly assigned to 400 µg folic acid and 500 µg vitamin B12 or placebo daily for 2 years. Global and domain-specific cognitive functioning were assessed at baseline and after 2 years. The effect of B-vitamin supplementation was analyzed according to tertiles of baseline plasma omega-3 fatty acids concentrations combined, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) individually using multiple linear regression analyses. RESULTS: The mean ± SD age of the participants was 71.6 ± 5.9 years and median [IQR] Mini-Mental State Examination was 29 [28-30]. The treatment effect of B-vitamins on global cognition was larger in participants in the high compared to the middle DHA tertile (difference in z-score, mean ± SE 0.22 ± 0.10, p = 0.03). There was no significant interaction between B-vitamin supplementation and combined omega-3 fatty acid (p = 0.49) and EPA (p = 0.99) tertiles. Similarly, the efficacy of B-vitamin treatment on domain-specific cognitive functioning did not link to omega-3 fatty acid, DHA, or EPA plasma levels. CONCLUSION: This post-hoc analysis indicated that efficacy of B-vitamin supplementation in slowing cognitive decline relates to DHA status, with individuals with higher plasma DHA levels benefitting more from vitamin B12 and folic acid use. The results support earlier observations that positive effects of B-vitamins in cognitive ageing may be subgroup-specific. TRIAL REGISTRATION: Registered at clinicaltrials.gov (NCT00696514) on June 12, 2008.

Bioactive Components in Traditional Foods Aimed at Health Promotion: A Route to Novel Mechanistic Insights and Lead Molecules?

Traditional foods and diets can provide health benefits beyond their nutrient composition because of the presence of bioactive compounds. In various traditional healthcare systems, diet-based approaches have always played an important role, which has often survived until today. Therefore, investigating traditional foods aimed at health promotion could render not only novel bioactive substances but also mechanistic insights. However, compared to pharmacologically focused research on natural products, investigating such nutrition-based interventions is even more complicated owing to interacting compounds, less potent and relatively subtle effects, the food matrix, and variations in composition and intake. At the same time, technical advances in 'omics' technologies, cheminformatics, and big data analysis create new opportunities, further strengthened by increasing insights into the biology of health and homeostatic resilience. These are to be combined with state-of-the-art ethnobotanical research, which is key to obtaining reliable and reproducible data. Unfortunately, socioeconomic developments and climate change threaten traditional use and knowledge as well as biodiversity.

Prevalence of Micronutrient Deficiencies and Relationship with Clinical and Patient-Related Outcomes in Pulmonary Hypertension Types I and IV.

BACKGROUND: Pulmonary hypertension (PH) is a rare progressive and lethal disease affecting pulmonary arteries and heart function. The disease may compromise the nutritional status of the patient, which impairs their physical performance. This study aimed to determine the prevalence of micronutrient deficiencies in pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension (CTEPH) patients. METHODS: Eighty-one blood samples from a prospective observational cohort study were analyzed for concentrations of micronutrients and inflammation-related factors. The samples consisted of newly diagnosed (treatment-naive) PAH and CTEPH patients and patients treated for 1.5 years according to ERS/ESC guidelines. RESULTS: In the newly diagnosed group, 42% of PAH patients and 21% of CTEPH patients were iron deficient compared to 29% of PAH patients and 20% of CTEPH patients in the treatment group. Vitamin D deficiency occurred in 42% of the newly diagnosed PAH patients, 71% of the newly diagnosed CTEPH patients, 68% of the treated PAH patients, and 70% of the treated CTEPH patients. Iron levels correlated with the 6 min walking distance (6MWD). CONCLUSIONS: Iron and vitamin D deficiencies are highly prevalent in PAH and CTEPH patients, underlining the need for monitoring their status. Studies evaluating the effects of supplementation strategies for iron and vitamin D are necessary.

Effects of Nutrients on Platelet Function: A Modifiable Link between Metabolic Syndrome and Neurodegeneration?

Metabolic syndrome increases the risk of vascular dementia and other neurodegenerative disorders. Recent studies underline that platelets play an important role in linking peripheral with central metabolic and inflammatory mechanisms. In this narrative review, we address the activation of platelets in metabolic syndrome, their effects on neuronal processes and the role of the mediators (e.g., serotonin, platelet-derived growth factor). Emerging evidence shows that nutritional compounds and their metabolites modulate these interactions-specifically, long chain fatty acids, endocannabinoids and phenolic compounds. We reviewed the role of activated platelets in neurovascular processes and nutritional compounds in platelet activation.

Positive effects of folic acid supplementation on cognitive aging are dependent on ω-3 fatty acid status: a post hoc analysis of the FACIT trial.

BACKGROUND: Although epidemiological studies suggest a protective role of B vitamins and omega-3 (ω-3) fatty acids in cognitive decline, findings from intervention studies are conflicting. Mechanistic studies suggest that the ω-3 (n-3) fatty acid status can modulate the effects of B vitamins on cognitive decline. OBJECTIVES: We investigated the interaction between baseline ω-3 fatty acid statuses and folic acid treatment on cognitive decline in a placebo-controlled trial [FACIT (Folic Acid and Carotid Intima-media Thickness)]. METHODS: This post hoc analysis included 791 older adults aged 50-70 y with plasma total homocysteine ≥13 µmol/L and ≤26 µmol/L and serum vitamin B12 ≥200 pmol/L. Participants received 800 µg folic acid or placebo daily for 3 y. Global cognitive functioning and domain-specific functioning (episodic memory, information processing speed, executive functioning) were assessed at baseline and after 3 y. The effect of the folic acid supplementation was analyzed according to tertiles of baseline ω-3 fatty acid concentrations using linear multiple regression. RESULTS: The mean ± SD age of the study population was 60.2 ± 5.6 y, and the mean ± SD Mini-Mental State Examination score was 28.6 ± 1.5. The treatment effect of folic acid was significantly larger in participants in the low compared to high ω-3 fatty acid tertile for global cognition (difference in z-score: mean ± SE = 0.16 ± 0.059; P < 0.01). Regarding domain-specific functioning, similar results were observed for information processing speed (mean ± SE = 0.167 ± 0.068; P = 0.01). There were no overall interactions between folic acid treatment and ω-3 fatty acid tertiles for episodic memory (P = 0.14) and executive functioning (P = 0.21). CONCLUSIONS: This post hoc analysis revealed that the efficacy of folic acid treatment on cognitive functioning is dependent on the ω-3 fatty acid status. Individuals with a lower ω-3 fatty acid status at baseline benefited from folic acid treatment, while individuals with a higher ω-3 fatty acid status did not. The results potentially explain the inconsistency in outcomes of B-vitamin supplementation trials and emphasize the importance of a personalized approach. This trial was registered at clinicaltrials.gov as NCT00110604.

Development and validation of a UPLC-MS/MS method for the simultaneous determination of gamma-aminobutyric acid and glutamic acid in human plasma.

Gamma-aminobutyric acid (GABA) and its precursor glutamic acid are important neurotransmitters. Both are also present in peripheral tissues and the circulation, where abnormal plasma concentrations have been linked to specific mental disorders. In addition to endogenous synthesis, GABA and glutamic acid can be obtained from dietary sources. An increasing number of studies suggest beneficial cardio-metabolic effects of GABA intake, and therefore GABA is being marketed as a food supplement. The need for further research into their health effects merits accurate and sensitive methods to analyze GABA and glutamic acid in plasma. To this end, an ultra-pressure liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of GABA and glutamic acid in human plasma. Samples were prepared by a protein precipitation step and subsequent solid phase extraction using acetonitrile. Chromatographic separation was achieved on an Acquity UPLC HSS reversed phase C18 column using gradient elution. Analytes were detected using electrospray ionization and selective reaction monitoring. Standard curve concentrations for GABA ranged from 3.4 to 2500 ng/mL and for glutamic acid from 30.9 ng/mL to 22,500 ng/mL. Within- and between-day accuracy and precision were <10% in quality control samples at low, medium and high concentrations for both GABA and glutamic acid. GABA and glutamic acid were found to be stable in plasma after freeze-thaw cycles and up to 12 months of storage. The validated method was applied to human plasma from 17 volunteers. The observed concentrations ranged between 11.5 and 20.0 ng/ml and 2269 and 7625 ng/ml for respectively GABA and glutamic acid. The reported method is well suited for the measurement of plasma GABA and glutamic acid in pre-clinical or clinical studies.

Vitamin D, magnesium, calcium, and their interaction in relation to colorectal cancer recurrence and all-cause mortality.

BACKGROUND: Higher concentrations of 25-hydroxyvitamin D3 [25(OH)D3] at diagnosis are associated with a lower mortality risk in colorectal cancer (CRC) patients. However, magnesium and calcium are important in vitamin D metabolism. OBJECTIVES: We aimed to investigate 25(OH)D3, magnesium, or calcium and their interaction among patients with CRC in relation to recurrence and all-cause mortality. METHODS: The study population included 1169 newly diagnosed stage I-III CRC patients from 2 prospective cohorts. Associations between 25(OH)D3 concentrations, magnesium or calcium intake through diet and/or supplements at diagnosis, and recurrence and all-cause mortality were evaluated using multivariable Cox proportional hazard models. The interaction between 25(OH)D3 and magnesium or calcium was assessed by investigating 1) joint compared with separate effects, using a single reference category; and 2) the effect estimates of 1 factor across strata of another. RESULTS: Serum 25(OH)D3, calcium, and magnesium, alone and their interactions, were not associated with recurrence. Serum 25(OH)D3 concentrations seemed to be associated with all-cause mortality. An inverse association between magnesium intake (HRQ3 vs. Q1: 0.55; 95% CI: 0.32, 0.95 and HRQ4 vs. Q1: 0.65; 95% CI: 0.35, 1.21), but not calcium intake, and all-cause mortality was observed. When investigating the interaction between 25(OH)D3 and magnesium, we observed the lowest risk of all-cause mortality in patients with sufficient vitamin D concentrations (≥50 nmol/L) and a high magnesium intake (median split) (HR: 0.53; 95% CI: 0.31, 0.89) compared with patients who were vitamin D deficient (<50 nmol/L) and had a low magnesium intake. No interactions between calcium and vitamin D in relation to all-cause mortality were observed. CONCLUSIONS: Our findings suggest that the presence of an adequate status of 25(OH)D3 in combination with an adequate magnesium intake is essential in lowering the risk of mortality in CRC patients, yet the underlying mechanism should be studied. In addition, diet and lifestyle intervention studies are needed to confirm our findings. The COLON study was registered at clinicaltrials.gov as NCT03191110. The EnCoRe study was registered at trialregister.nl as NTR7099.

Chemotherapy and vitamin D supplement use are determinants of serum 25-hydroxyvitamin D levels during the first six months after colorectal cancer diagnosis.

Vitamin D metabolites, including 25-hydroxyvitamin D3 (25(OH)D3), may inhibit colorectal cancer (CRC) progression. Here we investigated cross-sectional and longitudinal associations of demographic, lifestyle and clinical characteristics with 25(OH)D3 serum concentrations in CRC patients at diagnosis and six months later. In 1201 newly-diagnosed stage I-III CRC patients, 25(OH)D3 levels were analysed twice. Multivariable linear regression was used to assess demographic, lifestyle and clinical determinants of 25(OH)D3 levels at diagnosis and six months later. Linear mixed models were used to assess characteristics associated with changes in 25(OH)D3 levels over time. Results of our study showed that vitamin D intake from diet or supplements, use of calcium supplements, BMI and disease stage were associated with 25(OH)D3 levels at both time points. Six months after diagnosis, gender and having received chemo- and/or radiotherapy were also associated with 25(OH)D3 levels. A stronger decrease in 25(OH)D3 levels was observed in patients who underwent chemotherapy, compared to surgery only (ß-6.9 nmol/L 95 %CI -9.8; -4.0). Levels of 25(OH)D3 levels increased in patients using vitamin D supplements compared to non-users (ß 4.0 nmol/L 95 %CI 1.2; 6.8). In conclusion, vitamin D supplement use and treatment appear to be important determinants of 25(OH)D3 levels during the first six months after CRC diagnosis, although the difference in 25(OH)D3 levels was minor. ClinicalTrials.gov Identifier: NCT03191110.

A Diet Rich in Fish Oil and Leucine Ameliorates Hypercalcemia in Tumour-Induced Cachectic Mice.

BACKGROUND: Dietary supplementation with leucine and fish oil rich in omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) has previously been shown to reduce cachexia-related outcomes in C26 tumour-bearing mice. To further explore associated processes and mechanisms we investigated changes in plasma Ca2+ levels, the involvement of parathyroid hormone related protein (PTHrP), and its possible interactions with cyclooxygenase 2 (COX-2). METHODS: CD2F1 mice were subcutaneously inoculated with C26 adenocarcinoma cells or sham treated and divided in: (1) controls, (2) tumour-bearing controls, and (3) tumour-bearing receiving experimental diets. After 20 days, body and organ masses and total plasma Ca2+ levels were determined. Furthermore, effects of DHA, EPA and leucine on production of PTHrP were studied in cultured C26 cells. RESULTS: The combination of leucine and fish oil reduced tumour-associated hypercalcemia. Plasma Ca2+ levels negatively correlated with carcass mass and multiple organ masses. DHA was able to reduce PTHrP production by C26 cells in vitro. Results indicate that this effect occurred independently of COX-2 inhibition. CONCLUSION: Our results suggest that cancer-related hypercalcemia may be ameliorated by a nutritional intervention rich in leucine and fish oil. The effect of fish oil possibly relates to a DHA-induced reduction of PTHrP excretion by the tumour.

Increasing quality of life in pulmonary arterial hypertension: is there a role for nutrition?

Pulmonary arterial hypertension (PAH) is a progressive disease primarily affecting the pulmonary vasculature and heart. PAH patients suffer from exercise intolerance and fatigue, negatively affecting their quality of life. This review summarizes current insights in the pathophysiological mechanisms underlying PAH. It zooms in on the potential involvement of nutritional status and micronutrient deficiencies on PAH exercise intolerance and fatigue, also summarizing the potential benefits of exercise and nutritional interventions. Pubmed/Medline, Scopus, and Web of Science were searched for publications on pathophysiological mechanisms of PAH negatively affecting physical activity potential and nutritional status, and for potential effects of interventions involving exercise or nutritional measures known to improve exercise intolerance. Pathophysiological processes that contribute to exercise intolerance and impaired quality of life of PAH patients include right ventricular dysfunction, inflammation, skeletal muscle alterations, and dysfunctional energy metabolism. PAH-related nutritional deficiencies and metabolic alterations have been linked to fatigue, exercise intolerance, and endothelial dysfunction. Available evidence suggests that exercise interventions can be effective in PAH patients to improve exercise tolerance and decrease fatigue. By contrast, knowledge on the prevalence of micronutrient deficiencies and the possible effects of nutritional interventions in PAH patients is limited. Although data on nutritional status and micronutrient deficiencies in PAH are scarce, the available knowledge, including that from adjacent fields, suggests that nutritional intervention to correct deficiencies and metabolic alterations may contribute to a reduction of disease burden.

Fish oil LC-PUFAs do not affect blood coagulation parameters and bleeding manifestations: Analysis of 8 clinical studies with selected patient groups on omega-3-enriched medical nutrition.

BACKGROUND & AIMS: The increased consumption of fish oil enriched-products exposes a wide diversity of people, including elderly and those with impaired health to relatively high amounts of n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs). There is an ongoing debate around the possible adverse effects of n-3 LC-PUFAs on bleeding risk, particularly relevant in people with a medical history of cardiovascular events or using antithrombotic drugs. METHODS: This analysis of 8 clinical intervention studies conducted with enteral medical nutrition products containing fish oil as a source of n-3 LC-PUFAs addresses the occurrence of bleeding-related adverse events and effects on key coagulation parameters (Prothrombin Time [PT], (activated) and Partial Thromboplastin Time [(a)PTT]). RESULTS: In all the patients considered (over 600 subjects treated with the active product in total), with moderate to severe disease, with or without concomitant use of antithrombotic agents, at home or in an Intensive Care Unit (ICU), no evidence of increased risk of bleeding with use of n-3 LC-PUFAs was observed. Furthermore there were no statistically significant changes from baseline in measured coagulation parameters. CONCLUSION: These findings further support the safe consumption of n-3 LC-PUFAs, even at short-term doses up to 10 g/day of eicosapentaenoic acid + docosahexaenoic acid (EPA + DHA) or consumed for up to 52 weeks above 1.5 g/day, in selected vulnerable and sensitive populations such as subjects with gastrointestinal cancer or patients in an ICU. We found no evidence to support any concern raised with regards to the application of n-3 LC-PUFAs and the potentially increased risk for the occurrence of adverse bleeding manifestations in these selected patient populations consuming fish oil enriched medical nutrition.

Public health relevance of drug-nutrition interactions.

The public health relevance of drug-nutrition interactions is currently highly undervalued and overlooked. This is particularly the case for elderly persons where multi-morbidity and consequently polypharmacy is very common. Vitamins and other micronutrients have central functions in metabolism, and their interactions with drugs may result in clinically relevant physiological impairments but possibly also in positive effects. On 12 April 2016, the University Medical Center Groningen (The Netherlands), as part of its Healthy Ageing program, organized a workshop on the public health relevance of drug-nutrient interactions. In this meeting, experts in the field presented results from recent studies on interactions between pharmaceuticals and nutrients, and discussed the role of nutrition for elderly, focusing on those persons receiving pharmaceutical treatment. This paper summarizes the proceedings of the symposium and provides an outlook for future research needs and public health measures. Since food, pharma and health are closely interconnected domains, awareness is needed in the medical community about the potential relevance of drug-nutrition interactions. Experts and stakeholders should advocate for the integration of drug-nutrition evaluations in the drug development process. Strategies for the individual patients should be developed, by installing drug review protocols, screening for malnutrition and integrating this topic into the general medical advice.

The role of hypothalamic inflammation, the hypothalamic-pituitary-adrenal axis and serotonin in the cancer anorexia-cachexia syndrome.

PURPOSE OF REVIEW: In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin. RECENT FINDINGS: The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1ß-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer. SUMMARY: Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.

Intraileal casein infusion increases plasma concentrations of amino acids in humans: A randomized cross over trial.

BACKGROUND: Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. OBJECTIVE: To investigate the effects of intraileal infusion of native casein on plasma amino acid appearance, immune activation and gastrointestinal (GI) symptoms. DESIGN: A randomized single-blind cross over study was performed in 13 healthy subjects (6 male; mean age 26 ± 2.9 years; mean body mass index 22.8 ± 0.4 kg/m-2), who were intubated with a naso-ileal feeding catheter. Thirty minutes after intake of a standardized breakfast, participants received an ileal infusion, containing either control (C) consisting of saline, a low-dose (17.2 kcal) casein (LP) or a high-dose (51.7 kcal) of casein (HP) over a period of 90 min. Blood samples were collected for analysis of amino acids (AAs), C-reactive protein (CRP), pro-inflammatory cytokines and oxylipins at regular intervals. Furthermore, GI symptom questionnaires were collected before, during and after ileal infusion. RESULTS: None of the subjects reported any GI symptoms before, during or after ileal infusion of C, LP and HP. Plasma concentrations of all AAs analyzed were significantly increased after infusion of HP as compared to C (p < 0.001), and most AAs were increased after infusion of LP (p < 0.001). In total, 12.49 ± 1.73 and 3.18 ± 0.87 g AAs were found in plasma after intraileal infusion of HP and LP, corresponding to 93 ± 13% (HP) and 72 ± 20% (LP) of AAs infused as casein, respectively. Ileal casein infusion did not affect plasma concentrations of CRP, IL-6, IL-8, IL-1ß and TNF-α. Infusion of HP resulted in a decreased concentration of 11,12-dihydroxyeicosatrienoic acid whereas none of the other oxylipins analyzed were affected. CONCLUSIONS: A single intraileal infusion of native casein results in a concentration and time dependent increase of AAs in plasma, suggesting an effective digestion and absorption of AAs present in casein. Also, ileal infusion did not result in immune activation nor in GI symptoms. CLINICALTRIALS.GOV: NCT01509469.

Nutritional Supplement Use by Dutch Elite and Sub-Elite Athletes: Does Receiving Dietary Counseling Make a Difference?

The use of nutritional supplements is highly prevalent among athletes. In this cross-sectional study, we assessed the prevalence of nutritional supplement use by a large group of Dutch competitive athletes in relation to dietary counseling. A total of 778 athletes (407 males and 371 females) completed a web-based questionnaire about the use of nutritional supplements. Log-binomial regression models were applied to estimate crude and adjusted prevalence ratios (PR) for the use of individual nutritional supplements in athletes receiving dietary counseling as compared with athletes not receiving dietary counseling. Of the athletes, 97.2% had used nutritional supplements at some time during their sports career, whereas 84.7% indicated having used supplements during the last 4 weeks. The top ranked supplements used over the last 4 weeks from dietary supplements, sport nutrition products and ergogenic supplements were multivitamin and mineral preparations (42.9%), isotonic sports drinks (44.1%) and caffeine (13.0%). After adjustment for elite status, age, and weekly exercise duration, dietary counseling was associated with a higher prevalence of the use of vitamin D, recovery drinks, energy bars, isotonic drinks with protein, dextrose, beta-alanine, and sodium bicarbonate. In contrast, dietary counseling was inversely associated with the use of combivitamins, calcium, vitamin E, vitamin B2, retinol, energy drinks and BCAA and other amino acids. In conclusion, almost all athletes had used nutritional supplements at some time during their athletic career. Receiving dietary counseling seemed to result in better-informed choices with respect to the use of nutritional supplements related to performance, recovery, and health.

Decrease in Ionized and Total Magnesium Blood Concentrations in Endurance Athletes Following an Exercise Bout Restores within Hours-Potential Consequences for Monitoring and Supplementation.

Magnesium is essential for optimal sport performance, generating an interest to monitor its status in athletes. However, before measuring magnesium status in blood could become routine, more insight into its diurnal fluctuations and effects of exercise itself is necessary. Therefore, we measured the effect of an acute bout of exercise on ionized (iMg) and total plasma magnesium (tMg) in blood obtained from 18 healthy well-trained endurance athletes (age, 31.1 ± 8.1 yr.; VO2max, 50.9 ± 7.5 ml/kg/min) at multiple time points, and compared this with a resting situation. At both days, 7 blood samples were taken at set time points (8:30 fasted, 11:00, 12:30, 13:30, 15:00, 16:00, 18:30). The control day was included to correct for a putative diurnal fluctuation of magnesium. During the exercise day, athletes performed a 90 min bicycle ergometer test (70% VO2max) between 11:00 and 12:30. Whole blood samples were analyzed for iMg and plasma for tMg concentrations. Both concentrations decreased significantly after exercise (0.52 ± 0.04-0.45 ± 0.03 mmol/L and 0.81 ± 0.07-0.73 ± 0.06 mmol/L, respectively, p < .001) while no significant decline was observed during that time-interval on control days. Both, iMg and tMg, returned to baseline, on average, 2.5 hr after exercise. These findings suggest that timing of blood sampling to analyze Mg status is important. Additional research is needed to establish the recovery time after different types of exercise to come to a general advice regarding the timing of magnesium status assessment in practice.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155µM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30µM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100µM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10µM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.

Nutrient Intake by Ultramarathon Runners: Can They Meet Recommendations?

PURPOSE: The objective of this study was to investigate whether ultramarathon runners were able to meet nutrition recommendations during a training period and on a competition day. METHODS: In preparation for a 60 or 120 km ultramarathon covering a varied terrain, male and female ultramarathon runners (n = 68, age 46.5 ± 7.1 y) reported habitual dietary intake during three independent days using a web-based 24-hr recall and questionnaires. The diet was assessed using probability of inadequacy or by qualitative evaluation using reference dietary intakes or sports nutrition recommendations. A small group of 120 km runners (n = 4) was observed continuously during the race. After the race, 60 km runners (n = 41) received a questionnaire to assess dietary intake and gastrointestinal (GI) distress on the race day. Spearman rank correlation coefficients (r) were applied to investigate the association between intake and general GI distress symptoms. RESULTS: In men and women, habitual mean carbohydrate (CHO) intake was lower than recommended, as was mean protein intake by women. CHO intake during the race was <60 g/h in 75% of the athletes. A large variation of nutrient and fluid intake was seen. GI distress during the race was reported in 82% of the runners; severe GI distress was low. In general, moderate, mostly negative, correlations with nutrient intake were seen for GI distress. CONCLUSION: Sports nutrition recommendations for the habitual diet were not achieved. During a competition day, a large variation was found in nutrient intake; this may be related to a high incidence of GI distress.