Gut Endurance. Overview

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1 Gut Endurance Dr Justin Roberts Anglia Ruskin University, Cambridge Centre for Sport and Exercise Sciences Nutrition, Physical Activity and Health Research Group 1. GI issues Overview 2. How does exercise affect the gut? 3. Gut permeability 4. Endotoxins 5. Nutrition and GI Complaints 6. Can the gut be trained? 7. Beneficial effect of probiotics 8. Other nutritional factors 1

2 Is the GI System Built for Exercise? Exercise leads to reduced blood flow to GI tract Exercise = hypovolemia, hyperthermia, hyponatremia, hypotension, thermal injury The gut not an athletic organ Maybe this is all relative to how demanding the response is on an individual level? What is severe exercise? Gisolfi, C.V. (2000) News Physiol. Sci. 15 (6): Some questions raised? The gut is highly adaptive so is this a real issue? The gut can also signal conditions of impending injury therefore of benefit? Combination effect what if exercising in hot, prolonged, dehydrated state? Ischemia, hypoxia and hyperthermia effects? 2

3 1. GI issues Affects 30-50% of athletes Often overlooked Mainly endurance or exhaustive events Usually mild and transient Impact on training recovery and performance Acute: increased GI motility Chronic: functional GI stress More marathons are won or lost in the portatoilets than at the dinner table. (Bill Rodgers) Prado de Oliveira E. et al. (2014) Sports Medicine; 44 (1):S79-S85. GI Symptoms Varied severity amongst athletes Elite trained: 70-93% Mild-moderate Nausea common Discomfort, cramping Urgency, diarrhoea Vomiting Distance a key issue 4% marathon/cycling 32% ironman Severe Ischemic bowel Ischemic colitis Hemorrhagic gastritis Hematochezia (lower GI bleeding) Prado de Oliveira, E. and Jeukendrup, A. (2013). Sports Sci. Exchange; 26 (114): 1-4. Jeukendrup A. et al. (2000) Clin. Sci. (Lond.); 98: Peters H. et al. (1999) Am. J. Gastroenterol.; 94: Pfeiffer B. et al. (2012) Med. Sci. Sports Exerc.; 44:

4 GI Symptom Prevalence 161km Western States Ultramarathon 272 runners 96% reported some symptoms Race finishers: 43.9% GI related Non-finishers: 35.6% GI related Individual predisposition Nausea reduced appetite weight loss interplay Stuempfle, K. et al. (2015). J. Sports Sci.; 33(17): Causes of GI complaints? Physiological Mesenteric blood flow reduction Increased core temp Dehydration GI permeability Unaccustomed stomach distension Underlying H.Pylori Mechanical Symptoms more common in runners Repetitive GI impact Trauma/ microabrasions Cycling increased pressure? Core stability Air swallowing 4

5 2. How does exercise affect the gut? N=20 healthy volunteers 60mins cycling 70% max work capacity Small intestine epithelial damage Lack of reperfusion injury during recovery (intensity related) Evidence of gut tolerance to damage Van Wijck, K. et al. (2011). PlosOne; 6 (7): e GI Ischemia Varied GI hypoperfusion Lower GI hypoxia Oxidative damage Epithelial injury TJ dysfunction Ischemic colitis Infarct or necrotic tissue Hydrogen peroxide linked Zuhl, M. et al. (2014). Br. J. Sports Med.; 48: Heer, M. et al. (1987). Gut; 28:

6 3. But is there any evidence of GI permeability? Noradrenaline splanchnic vasoconstriction Reduced blood flow (HI - 80%) Increased vascular resistance Paracellular transport disrupted Sustained intensity or acute disruption? Lambert G. et al. (2002). J. Appl. Physiol.; 92: ; Pals, K. et al. (1997). J. Appl. Physiol.; 82 (2): What about possible dehydration? Dehydration impacts on gut perfusion Implications for exercise 20 runners 60mins 70%VO 2max running With fluid:? Attenuated GI hypoperfusion? Attenuated GI hyperthermia Lambert, G. et al. (2008). Int. J. Sports Med.; 29:

7 Translocational dysfunction GI hyperthermia (>40 C) Cell sloughing Villi damage/shrinking Intestinal oedema Intestinal bleeding Lambert G. et al. (2002). Am. J. Physiol.; 92: Lambert, G. (2009). J. Anim. Sci.; 87 (E. Suppl.): E101-E Endotoxins LPS translocation Systemic endotoxin release Lymphocyte TLR4 attachment CD14 receptors Inflammatory cascade (TNF-α, IL-1β, IL-6, CRP) Abdominal cramping, nausea, vomiting Na/K pump damage on basolateral membrane Reduced fluid absorption Reverse fluid accumulation Diarrhoea Zuhl, M. et al. (2014). Br. J. Sports Med.; 48:

8 Exhaustive endotoxemia Comrades marathon (n=89) 81% reported as endotoxemic 80.6% with EU reported nausea, diarrhea and vomiting LPS values appear very high 1-3 weeks recovery Increased anti-lps IgG concentrations Brock-Utne, J. et al. (1988). S. Afr. Med. J.; 73: Recovery and endotoxins 5-15 pg.ml -1 reported in 68% of athletes 20 fold increase in CRP 93% reported GI symptoms 45% severe 7% abandoned race EU did not correlate with GI complaints EU correlated with CRP Jeukendrup A. et al. (2000) Clin. Sci. (Lond.); 98:

9 Associated GI distress and endotoxemia Western States Ultra 30 runners, 20 finished Endotoxemia (scd14 not LPS) GI symptoms 80% High correlation between nausea severity and endotoxemia Hyperthermia, dehydration and diet not related Stuempfle, K. et al. (2015). J. Sports Sci.; 28: Nutrition and GI Complaints Nutritional pre Dysbiotic state Pre training choices High fat intake Fiber Protein Use of NSAIDs Nutritional during Fructose and high osmolarity solutions Carbohydrate gels/ food Issue of water/food balance Amar, J. et al. (2008). Am. J. Clin. Nutr.; 87: Erridge, C. et al. (2007). Am. J. Clin. Nutr.; 86:

10 Influence of gastric emptying GE related to intragastric pressure Energy density and volume Water and CHO delivery appears unaffected up to ~70%VO 2 max HI or intermittent exercise Reduced emptying (~50%) Extreme temperatures/ hyperthermia/ dehydration reduce GE CHO = gastric emptying - fluid for absorption Decreased esophageal peristaltic activity Thus volumes ingested should be <250ml to minimise fullness Murray, R. et al. (1999). Int. J. Sport Nutrition; 9: Carbohydrate influence? 7 active participants 60mins running at 70%VO 2max 30 C 27g gel at 20mins TNF-α increased post exercise with gel Activation of SGLT-1 triggering perijunctional actomyosin contraction Sessions, J. et al. (2016). Eur. J. Sports Sci.; 2:

11 6. Can the gut be trained? Periodised nutrition approaches Improved distension tolerance Increased exercise comfort 28 day high CHO diet (8.5g/kg) associated with higher CHO oxidation during exercise Cox, G. et al. (2010). J. Appl. Physiol.; 109: Time TOT CHOox (g.min -1 ) EXO CHOox (g.min -1 ) TOT FATox (g.min -1 ) Roberts, J., Furber, M. and Roberts, M. (2012) Laboratory observations of a world record ironman athlete Haile Gebrselassie 2:06:35 no water; :03: g/hr Stellingworth, T. (2012). Int. J. Sport Nutrition Exerc. Metab.; 22:

12 Back to Gisolfi.. Improved gut barrier function with training? Increased GE Greater heat tolerance protection against EU leakage Maintenance of GI blood supply in fitter people? GI remarkably regenerative The gut is an athletic organ to a point What if athlete taking NSAIDs? What if prolonged or strenuous exercise? In the heat? What if dehydrated? But in background, microbiota has a role to play? Gisolfi, C.V. (2000) News Physiol. Sci. 15 (6): Beneficial effects of probiotics Lactic bacteria might activate TLR2 Epithelial resistance CFU/d 14 weeks Lactobacillus acidophilus Lactobacillus plantarum Bifidobacterium longum Lactobacillus rhamnosus Competitive biofilm activity Prevent phosphorylation of occludin Increased zonulin/actin cytoskeleton interaction Prebiotic synergy inulin Onions, bananas, oats, leeks, garlic Lamprecht, M. et al. (2012). J. Int. Soc. Sports Nutrition; 9:45. 12

13 Roberts, J.D. et al. (2016) Nutrients; 8(11), 733. Roberts, J.D. et al. (2016) Nutrients; 8(11),

14 Roberts, J.D. et al. (2016) Nutrients; 8(11), 733. Roberts, J.D. et al. (2016) Nutrients; 8(11),

15 Issues with term endotoxemia? Range: pg.ml -1 Hence some individuals may be more susceptible to repeated exposure Lactobacillus genus may provide a more favourable innate immune response by activating TLR2 Probiotic/antioxidant may minimise low grade cytokinemia from exercise Future research should address strain specific colonization, and inter-individual differences. Roberts, J.D. et al. (2016) Nutrients; 8(11), Other nutritional factors: colostrum Epithelial growth factor (EGF) Insulin-like growth factor-i and II (IGF-1 and IGF-II) Trypsin and protease inhibitors Oligo-polysaccharides and glycoconjugates affect E.Coli uptake Playford, R. et al. (2001). Clin. Sci.; 100: Prosser, C. et al. (2004). J. Appl. Physiol.; 96: Marchbank, T. et al. (2011). Am. J. Physiol. Gastrointest. Liver Physiol.; 300: G477-G

16 Use of L-glutamine Principal fuel and nitrogen source for enterocytes Intestinal extraction of glutamine ~13% Intestinal mucosal hyperplasia TJ resistance Glutamine-mediated increase in HSF-1 leading to HSP transcription Reduced proinflammatory cytokine release Benjamin, J. et al. (2012). Dig. Dis. Sci.; 57: Duggan, C. et al. (2002). Am. J. Clin. Nutr.; 75: Zinc Carnosine In animal model, ZnC stimulated migration and proliferation of cells in a dose dependent manner; 50% reduction in villi shortening ZnC beneficial in blunting the response to NSAIDs via L:R Proposed that carnosine (β-alanine/l-histidine) acts in an antioxidant manner Mahmood, A. et al. (2007). Gut; 56: Duggan, C. et al. (2002). Am. J. Clin. Nutr.; 75:

17 Use of antioxidants N=10 healthy volunteers V0 2max test 8 weeks later 2 hr pre Vit C supplementation Flavonoids (naringenin, hesperidin) suppress ROS Ashton, T. et al. (2003). Free Radical Biol. Med.; 35 (3): Ghanim, H. et al. (2010). Am. J. Clin. Nutr.; 91: Nutrients DHA and EPA attenuated endotoxin transport N-3 PUFA disrupt TLR4 and activation of NFkB by LPS Mani, V. et al. (2013). Nutr. Metabol.; 10:6. 17

18 Summary: my take 1. Gut is an athletic organ 2. Effects are highly individual 3. Likely due to acute severe exercise trauma 4. Microbiota diversity likely key 5. Susceptible individuals may need to consider nutritional preparation strategies 6. Use of pre/probiotic complexes 7. Potential for additive nutrients (antioxidants) 8. The gut can be trained nutritionally Functional Nutrition Strategies (considerations) Minimise/Eliminate Before Lower fat, fiber, protein content Total sugar load Lactose NSAIDs Caffeine Wheat/gluten During Single CHO/ fructose Positive/Interactive Before Probiotics Prebiotics Colostrum L-glutamine/ zinc Habitual flavonoids Anti-inflammatory diet (inc. EFAs) NO stimulation (nitrates) Low residual/ FODMAPs During Multiple transportable CHO Maintain hydration intake 18

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