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Contains fulltext : 215418.pdf (Publisher’s version ) (Closed access) BACKGROUND: Hypomagnesemia has been associated with diabetes, cardiovascular disease, and other disorders. Drug use has been suggested as one of the risk factors for low magnesium (Mg) levels. In the elderly population, prone to polypharmacy and inadequate Mg intake, hypomagnesemia might be relevant. Therefore, we aimed to investigate associations between drug use and plasma Mg. METHODS: Cross-sectional data of 343 Dutch geriatric outpatients were analysed by Cox and linear regression, while adjusting for covariates. Drug groups were coded according to the Anatomical Therapeutic Chemical classification system; use was compared to non-use. Hypomagnesemia was defined as plasma Mg < 0.75 mmol/l and /=5 medications (polypharmacy). The number of different drugs used was inversely linearly associated with Mg level (beta -0.01; p < 0.01). Fully adjusted Cox regression showed significant associations of polypharmacy with hypomagnesemia (Mg < 0.75 mmol/l) (prevalence ratio (PR) 1.81; 95%CI 1.08-3.14), proton pump inhibitors (PR 1.80; 95%CI 1.20-2.72), and metformin (PR 2.34; 95%CI 1.56-3.50). Moreover, stratified analyses pointed towards associations with calcium supplements (PR 2.26; 95%CI 1.20-4.26), insulins (PR 3.88; 95%CI 2.19-6.86), vitamin K antagonists (PR 2.01; 95%CI 1.05-3.85), statins (PR 2.44; 95%CI 1.31-4.56), and bisphosphonates (PR 2.97; 95%CI 1.65-5.36) in patients

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-1beta and TNF-alpha. 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.

Rationale: Metabolic stress like surgery and intensive exercise have been reported to increase intestinal permeability. It is not known whether intensive exercise also influences gut metabolic functioning. The effects of intensive exercise on intestinal permeability, postprandial amino acid (AA) bioavailability and intestinal enterocyte metabolic mass were determined in the human intervention study Protege.