Daniel Scott March

Zinc carnosine works with bovine colostrum in truncating heavy exercise–induced increase in gut permeability in healthy volunteers

BACKGROUND Heavy exercise causes gut symptoms and, in extreme cases, heat stroke that is due to the increased intestinal permeability of luminal toxins. OBJECTIVE We examined whether zinc carnosine (ZnC), a health-food product taken alone or in combination with bovine colostrum (a natural source of growth factors), would moderate such effects. DESIGN Eight volunteers completed a 4-arm, double-blind, placebo-controlled crossover protocol (14 d of placebo, ZnC, colostrum, or ZnC plus colostrum) before undertaking standardized exercise 2 and 14 d after the start of treatment. Changes in epithelial resistance, apoptosis signaling molecules, and tight junction (TJ) protein phosphorylation in response to a 2°C rise in body temperature were determined with the use of Caco-2 and HT29 intestinal cells. RESULTS Body temperature increased 2°C, and gut permeability (5-h urinary lactulose:rhamnose ratios) increased 3-fold after exercise (from 0.32 ± 0.016 baseline to 1.0 ± 0.017 at 14 d; P < 0.01). ZnC or colostrum truncated the rise by 70% after 14 d of treatment. The combination treatment gave an additional benefit, and truncated exercise induced increase at 2 d (30% reduction; P < 0.01). A 2°C temperature rise in in vitro studies caused the doubling of apoptosis and reduced epithelial resistance 3-4-fold. ZnC or colostrum truncated these effects (35-50%) with the greatest response seen with the combination treatment (all P < 0.01). Mechanisms of action included increasing heat shock protein 70 and truncating temperature-induced changes in B cell leukemia/lymphoma-2 associated X protein α and B cell lymphoma 2. ZnC also increased total occludin and reduced phosphorylated tyrosine claudin, phosphorylated tyrosine occludin, and phosphorylated serine occludin, thereby enhancing the TJ formation and stabilization. CONCLUSION ZnC, taken alone or with colostrum, increased epithelial resistance and the TJ structure and may have value for athletes and in the prevention of heat stroke in military personnel. This trial was registered at www.isrctn.com as ISRCTN51159138.

The Potential Cardiovascular Benefits of Low-Glucose Degradation Product, Biocompatible Peritoneal Dialysis Fluids: A Review of the Literature.

Cardiovascular mortality in the end-stage renal disease (ESRD) population remains the leading cause of death. Targeting traditional cardiovascular risk factors has proven unsuccessful in this patient population, and therefore attention has turned to risk factors related to chronic kidney disease (CKD). The toxicity of high-glucose peritoneal dialysis (PD) solutions has been well documented. The breakdown of glucose into glucose degradation products (GDP) and advanced glycation end-products (AGE) has the ability to alter cell viability and cause premature apoptosis and is strongly correlated with interstitial fibrosis and microvascular sclerosis. Biocompatible solutions have been introduced to combat the hostile milieu to which PD patients are exposed. Given the considerable cardiovascular burden for PD patients, little is known about the cardiovascular impact the new biocompatible solutions may have. This review analyzes the existing literature regarding the mechanisms through which low-GDP solutions may modulate cardiovascular risk. Interventions using low-GDP solutions have provided encouraging changes in structural cardiovascular measures such as left ventricular mass (LVM), although metabolic changes from reduced GDP and AGE exposure yield inconclusive results on vascular remodelling. It is thought that the local effects of reduced glucose exposure may improve membrane integrity and therefore fluid status. Further research in the form of a robust randomized controlled trial should be carried out to assess the true extent of the cardiovascular benefits these biocompatible solutions may hold.

Intestinal Barrier Disturbances in Haemodialysis Patients: Mechanisms, Consequences, and Therapeutic Options

There is accumulating evidence that the intestinal barrier and the microbiota may play a role in the systemic inflammation present in HD patients. HD patients are subject to a number of unique factors, some related to the HD process and others simply to the uraemic milieu but with common characteristic that they can both alter the intestinal barrier and the microbiota. This review is intended to provide an overview of the current methods for measuring such changes in HD patients, the mechanisms behind these changes, and potential strategies that may mitigate these modifications. Lastly, intradialytic exercise is an increasingly employed intervention in HD patients; however the potential implications that this may have for the intestinal barrier are not known; therefore future research directions are also covered.

Influence of 4 weeks of bovine colostrum supplementation on neutrophil and mucosal immune responses to prolonged cycling

Bovine colostrum (COL) has been advocated as a nutritional countermeasure to exercise‐induced immune dysfunction. The aims of this study were to identify the effects of 4 weeks of COL supplementation on neutrophil responses and mucosal immunity following prolonged exercise. In a randomized double‐blind, parallel group design, participants [age 28 ± 8 years; body mass 79 ± 7 kg; height 182 ± 6 cm; maximal oxygen uptake ( V ˙ O 2 m a x ) 55 ± 9 mL/kg/min] were assigned to 20 g per day of COL (n = 10) or an isoenergetic/isomacronutrient placebo (PLA; n = 10) for 4 weeks. Venous blood and unstimulated saliva samples were obtained before and after 2.5 h of cycling at 15% Δ (∼55–60% V ˙ O 2 m a x ). A significantly greater formyl‐methionyl‐leucyl phenylalanine‐stimulated oxidative burst was observed in the COL group compared with PLA group (P < 0.05) and a trend toward a time × group interaction (P = 0.06). However, there was no effect of COL on leukocyte trafficking, phorbol‐12‐myristate‐13‐acetate‐stimulated oxidative burst, bacterial‐stimulated neutrophil degranulation, salivary secretory IgA, lactoferrin or lysozyme (P > 0.05). These findings provide further evidence of the beneficial effects of COL on receptor‐mediated stimulation of neutrophil oxidative burst in a model of exercise‐induced immune dysfunction.

Imaging of Myocardial Fibrosis in Patients with End-Stage Renal Disease: Current Limitations and Future Possibilities.

Cardiovascular disease in patients with end-stage renal disease (ESRD) is driven by a different set of processes than in the general population. These processes lead to pathological changes in cardiac structure and function that include the development of left ventricular hypertrophy and left ventricular dilatation and the development of myocardial fibrosis. Reduction in left ventricular hypertrophy has been the established goal of many interventional trials in patients with chronic kidney disease, but a recent systematic review has questioned whether reduction of left ventricular hypertrophy improves cardiovascular mortality as previously thought. The development of novel imaging biomarkers that link to cardiovascular outcomes and that are specific to the disease processes in ESRD is therefore required. Postmortem studies of patients with ESRD on hemodialysis have shown that the extent of myocardial fibrosis is strongly linked to cardiovascular death and accurate imaging of myocardial fibrosis would be an attractive target as an imaging biomarker. In this article we will discuss the current imaging methods available to measure myocardial fibrosis in patients with ESRD, the reliability of the techniques, specific challenges and important limitations in patients with ESRD, and how to further develop the techniques we have so they are sufficiently robust for use in future clinical trials.

Effects of intradialytic cycling exercise on exercise capacity, quality of life, physical function and cardiovascular measures in adult haemodialysis patients: a systematic review and meta-analysis

Background Intradialytic cycling (IDC), delivered during haemodialysis (HD), has the potential to improve many health issues. This systematic review and meta-analysis examine the evidence on the effects of IDC on exercise capacity, quality of life (QoL), physical function and cardiovascular health. Methods Twenty-four databases were searched alongside Internet and hand searching, and consultation with experts. Eligibility criteria were cluster randomized, randomized and quasi-randomized controlled trials (RCTs) of IDC versus usual care in prevalent adult HD patients. Primary outcome measures were exercise capacity (VO2 peak and field tests) and QoL. Secondary measures were cardiac and physical function. Results Thirteen RCTs were eligible. Eight provided data for use in meta-analyses, which indicated no significant change in VO2 peak (mean difference, MD 1.19 mL/kg/min, 95% confidence interval -1.15 to 3.52, P = 0.3), physical (mean change, MC 1.97, -8.27 to 12.22, P = 0.7) or mental component (MC 3.37, -7.94 to 14.68, P = 0.6) summary scores of the Medical Outcomes Short Form 36, pulse wave velocity (MD -0.57 m/s, -1.55 to 0.41, P = 0.4), systolic (MD -2.28 mmHg, -14.46 to 9.90, P = 0.7) or diastolic blood pressure (MD 2.25 mmHg, -3.01 to 7.50, P = 0.4) following IDC. IDC, however, leads to an improvement in performance on the 6-min walk test (MD 87.84 m, 39.60-136.09, P = 0.0004). All included studies were considered to have high risk of bias. Conclusions There is insufficient evidence demonstrating whether cycling exercise during HD improves patient outcomes. High-quality, adequately powered RCTs of IDC are required.

‘There is nothing more deceptive than an obvious fact’: more evidence for the prescription of exercise during haemodialysis (intradialytic exercise) is still required

With regard to the recent editorial,1 we applaud the author’s call to arms for nephrologists to ‘prescribe’ exercise during haemodialysis (HD). It is true that exercise has tremendous health benefits, with many likely benefits for HD patients. Staying physically active is essential to maintaining health, and unquestionably clinicians caring for HD patients should be counselling patients to increase physical activity levels. There are, however, unresolved questions that must be answered before structured programmes of intradialytic exercise (IDE) can simply be ‘prescribed’ by clinicians, as Deschamps suggests. The UK Renal Association clinical practice guidelines for cardiovascular disease state that exercise should be encouraged for all HD patients,2 but practical recommendations on prescribing and dosing of exercise (and indeed safest modes of exercise) cannot currently be made based on the available evidence. …

OC-023 Randomised Trial: The Nutriceutical Zinc Carnosine Works with Bovine Colostrum in Truncating Heavy Exercise Induced Increase in Gut Permeability through Actions on Tight Junctions, Apoptosis and Heat Shock Protein 70 Production

Introduction Heavy exercise causes gut symptoms and, in extreme cases, “heat stroke” due to increased intestinal permeability of luminal toxins. We examined whether zinc carnosine (ZnC) a health food product taken alone or in combination with bovine colostrum, a natural source of growth factors, moderated such effects. Methods 8 volunteers completed a four-arm double-blind, placebo-controlled, crossover protocol (14 days placebo, ZnC, colostrum, ZnC + colostrum) prior to standardised exercise undertaken 2 and 14 days after starting treatment. Changes in epithelial resistance, apoptosis signalling molecules and tight junction protein phosphorylation in response to 20 C rise were determined using Caco-2 & HT29 intestinal cells. Results Body temperature increased 20 C and gut permeability (5 h urinary lactulose:rhamnose ratios) increased 3 fold following exercise (0.32 ± 0.016 baseline to 1.0 ± 0.017 at +14 days, p < 0.01). ZnC or colostrum truncated rise by 70% after 14 days treatment. Combination treatment gave additional benefit and truncated exercise induced increase at +2 day (30% reduction, p < 0.01) 2°C temperature rise in in vitro studies caused doubling of apoptosis and reduced epithelial resistance 3–4 fold. ZnC or colostrum truncated these effects (35–50%) with greatest response seen with combination treatment (all p < 0.01). Mechanisms of action included increasing HSP70 and truncating temperature-induced changes in Baxα and Bcl-2. ZnC also increased total occludin and reduced pTyr-claudin, pTyr-occludin and pSer-occludin, enhancing tight junction formation and stabilisation. Conclusion ZnC taken alone or with colostrum increased epithelial resistance and tight junction structure and may have value for athletes and preventing heat stroke in military personnel. Disclosure of Interest None Declared