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Food as Therapy for Frailty

  • Nutrition in Patients with Chronic Liver Disease (E Tapper, Section Editor)
  • Published:
Current Hepatology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Frailty in end-stage liver disease is a risk factor for mortality and other serious complications for transplant-waitlist patients. Multiple interventions have been studied to try to mitigate these effects by targeting contributors to frailty, most notably sarcopenia and hepatic encephalopathy. This review provides an evidence-based summary of interventions that have been recommended to prevent or reverse frailty and its contributors.

Recent Findings

Current nutritional recommendations for frailty in end-stage liver disease focus on mitigating the effects of ammonia toxicity, increased energy expenditure due to shifts in glucose metabolism, and micronutrient deficiency and supplementation.

Summary

Data regarding targeted nutritional interventions for frailty in cirrhosis are limited. Current evidence supports increasing caloric intake, increasing protein intake, avoiding a fasting state, branched-chain amino acid supplementation, screening for and treating vitamin D deficiency, and to a lesser extent l-carnitine supplementation. Future randomized controlled trials are necessary to validate these interventions as modifiers of frailty.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146–56.

    Article  CAS  PubMed  Google Scholar 

  2. Xue Q-L. The frailty syndrome: definition and natural history. Clin Geriatr Med. 2011;27:1–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lai JC, Feng S, Terrault NA, Lizaola B, Hayssen H, Covinsky K. Frailty predicts waitlist mortality in liver transplant candidates: frailty in liver transplant candidates. Am J Transplant. 2014;14:1870–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dunn MA, Josbeno DA, Tevar AD, Rachakonda V, Ganesh SR, Schmotzer AR, et al. Frailty as tested by gait speed is an independent risk factor for cirrhosis complications that require hospitalization. Am J Gastroenterol. 2016;111:1768–75.

    Article  PubMed  Google Scholar 

  5. • Lai JC, Sonnenday CJ, Tapper EB, Duarte-Rojo A, Dunn MA, Bernal W, et al. Frailty in liver transplantation: an expert opinion statement from the American Society of Transplantation Liver and Intestinal Community of Practice. Am J Transplant. 2019;19:1896–906 An opinion statement released by experts in the field of frailty in end-stage liver disease advocating for the measurement of frailty in all liver transplant candidates using a standardized tool. Experts also advocated for the use of frailty to guide nutritional interventions and physical therapy, incorporating frailty in determining suitability for transplant, and future areas of research.

    PubMed  PubMed Central  Google Scholar 

  6. Tapper EB, Finkelstein D, Mittleman MA, Piatkowski G, Lai M. Standard assessments of frailty are validated predictors of mortality in hospitalized patients with cirrhosis: liver failure/cirrhosis/portal hypertension. Hepatology. 2015;62:584–90.

    Article  PubMed  Google Scholar 

  7. Montano-Loza AJ, Meza-Junco J, Baracos VE, Prado CMM, Ma M, Meeberg G, et al. Severe muscle depletion predicts postoperative length of stay but is not associated with survival after liver transplantation: sarcopenia after liver transplantation. Liver Transpl. 2014;20:640–8.

    Article  PubMed  Google Scholar 

  8. Englesbe MJ, Patel SP, He K, Lynch RJ, Schaubel DE, Harbaugh C, et al. Sarcopenia and mortality after liver transplantation. J Am Coll Surg. 2010;211:271–8.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Carey EJ, Lai JC, Wang CW, Dasarathy S, Lobach I, Montano-Loza AJ, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transpl. 2017;23:625–33.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tapper EB, Derstine B, Baki J, Su GL. Bedside measures of frailty and cognitive function correlate with sarcopenia in patients with cirrhosis. Dig Dis Sci. 2019;64(12):3652–9.

    Article  PubMed  Google Scholar 

  11. Tapper EB, Konerman M, Murphy S, Sonnenday CJ. Hepatic encephalopathy impacts the predictive value of the Fried Frailty Index. Am J Transplant. 2018;18:2566–70.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Lai JC, Covinsky KE, Dodge JL, Boscardin WJ, Segev DL, Roberts JP, et al. Development of a novel frailty index to predict mortality in patients with end-stage liver disease. Hepatology. 2017;66:564–74.

    Article  PubMed  Google Scholar 

  13. • Amodio P, Bemeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology. 2013;58:325–36 Evidence-based guidelines for nutritional interventions in patients with hepatic encephalopathy.

    Article  CAS  PubMed  Google Scholar 

  14. • Merli M, Berzigotti A, Zelber-Sagi S, Dasarathy S, Montagnese S, Genton L, et al. EASL clinical practice guidelines on nutrition in chronic liver disease. J Hepatol. 2019;70:172–93 Nutritional guidelines for patients with chronic liver disease. Presents evidence-based recommendations for patients with chronic liver disease, cirrhosis, and specific comorbidities such as hepatic encephalopathy, patients with concurrent bone disease, and critically ill cirrhotic patients.

    Article  Google Scholar 

  15. Carey EJ, Lai JC, Sonnenday C, Tapper EB, Tandon P, Duarte-Rojo A, et al. A North American expert opinion statement on sarcopenia in liver transplantation. Hepatology. 2019;70(5):1816–29.

    Article  PubMed  Google Scholar 

  16. Greco AV, Mingrone G, Benedetti G, Capristo E, Tataranni PA, Gasbarrini G. Daily energy and substrate metabolism in patients with cirrhosis. Hepatology. 1998;27:346–50.

    Article  CAS  PubMed  Google Scholar 

  17. Dasarathy S, Merli M. Sarcopenia from mechanism to diagnosis and treatment in liver disease. J Hepatol. 2016;65:1232–44.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Tsien CD, McCullough AJ, Dasarathy S. Late evening snack: exploiting a period of anabolic opportunity in cirrhosis. J Gastroenterol Hepatol. 2012;27:430–41.

    Article  CAS  PubMed  Google Scholar 

  19. Montano-Loza AJ, Angulo P, Meza-Junco J, Prado CMM, Sawyer MB, Beaumont C, et al. Sarcopenic obesity and myosteatosis are associated with higher mortality in patients with cirrhosis. J Cachexia Sarcopenia Muscle. 2016;7:126–35.

    Article  PubMed  Google Scholar 

  20. Everhart JE, Lok AS, Kim H-Y, Morgan TR, Lindsay KL, Chung RT, et al. Weight-related effects on disease progression in the hepatitis C antiviral long-term treatment against cirrhosis trial. Gastroenterology. 2009;137:549–57.

    Article  PubMed  Google Scholar 

  21. Guo Y-J, Tian Z-B, Jiang N, Ding X-L, Mao T, Jing X. Effects of late evening snack on cirrhotic patients: a systematic review and meta-analysis. Gastroenterol Res Pract. 2018;2018:9189062.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Fukushima H, Miwa Y, Ida E, Kuriyama S, Toda K, Shimomura Y, et al. Nocturnal branched-chain amino acid administration improves protein metabolism in patients with liver cirrhosis: comparison with daytime administration. JPEN J Parenter Enteral Nutr. 2003;27:315–22.

    Article  CAS  PubMed  Google Scholar 

  23. Yamanaka-Okumura H, Nakamura T, Takeuchi H, Miyake H, Katayama T, Arai H, et al. Effect of late evening snack with rice ball on energy metabolism in liver cirrhosis. Eur J Clin Nutr. 2006;60:1067–72.

    Article  CAS  PubMed  Google Scholar 

  24. Nakaya Y, Okita K, Suzuki K, Moriwaki H, Kato A, Miwa Y, et al. BCAA-enriched snack improves nutritional state of cirrhosis. Nutrition. 2007;23:113–20.

    Article  CAS  PubMed  Google Scholar 

  25. Korenaga K, Korenaga M, Uchida K, Yamasaki T, Sakaida I. Effects of a late evening snack combined with alpha-glucosidase inhibitor on liver cirrhosis. Hepatol Res. 2008;38:1087–97.

    Article  CAS  PubMed  Google Scholar 

  26. Plank LD, Gane EJ, Peng S, Muthu C, Mathur S, Gillanders L, et al. Nocturnal nutritional supplementation improves total body protein status of patients with liver cirrhosis: a randomized 12-month trial. Hepatology. 2008;48:557–66.

    Article  PubMed  Google Scholar 

  27. Yamanaka-Okumura H, Nakamura T, Miyake H, Takeuchi H, Katayama T, Morine Y, et al. Effect of long-term late-evening snack on health-related quality of life in cirrhotic patients. Hepatol Res. 2010;40:470–6.

    Article  PubMed  Google Scholar 

  28. Hiraoka A, Michitaka K, Kiguchi D, Izumoto H, Ueki H, Kaneto M, et al. Efficacy of branched-chain amino acid supplementation and walking exercise for preventing sarcopenia in patients with liver cirrhosis. Eur J Gastroenterol Hepatol. 2017;29:1416–23.

    Article  CAS  PubMed  Google Scholar 

  29. Riordan SM, Williams R. Treatment of hepatic encephalopathy. N Engl J Med. 1997;337:473–9.

    Article  CAS  PubMed  Google Scholar 

  30. Córdoba J, López-Hellín J, Planas M, Sabín P, Sanpedro F, Castro F, et al. Normal protein diet for episodic hepatic encephalopathy: results of a randomized study. J Hepatol. 2004;41:38–43.

    Article  PubMed  CAS  Google Scholar 

  31. Gheorghe L, Iacob R, Vădan R, Iacob S, Gheorghe C. Improvement of hepatic encephalopathy using a modified high-calorie high-protein diet. Rom J Gastroenterol. 2005;14:231–8.

    PubMed  Google Scholar 

  32. Swart GR, van den Berg JW, van Vuure JK, Rietveld T, Wattimena DL, Frenkel M. Minimum protein requirements in liver cirrhosis determined by nitrogen balance measurements at three levels of protein intake. Clin Nutr. 1989;8:329–36.

    Article  CAS  PubMed  Google Scholar 

  33. Weber FL, Minco D, Fresard KM, Banwell JG. Effects of vegetable diets on nitrogen metabolism in cirrhotic subjects. Gastroenterology. 1985;89:538–44.

    Article  CAS  PubMed  Google Scholar 

  34. Yoon M-S. mTOR as a key regulator in maintaining skeletal muscle mass. Front Physiol. 2017;8:788.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Qiu J, Tsien C, Thapalaya S, Narayanan A, Weihl CC, Ching JK, et al. Hyperammonemia-mediated autophagy in skeletal muscle contributes to sarcopenia of cirrhosis. Am J Physiol Endocrinol Metab. 2012;303:E983–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen H-W, Dunn MA. Muscle at risk: the multiple impacts of ammonia on sarcopenia and frailty in cirrhosis. Clin Transl Gastroenterol. 2016;7:e170.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Tsien C, Davuluri G, Singh D, Allawy A, Ten Have GAM, Thapaliya S, et al. Metabolic and molecular responses to leucine-enriched branched chain amino acid supplementation in the skeletal muscle of alcoholic cirrhosis. Hepatology. 2015;61:2018–29.

    Article  CAS  PubMed  Google Scholar 

  38. Leenders M, van Loon LJC. Leucine as a pharmaconutrient to prevent and treat sarcopenia and type 2 diabetes. Nutr Rev. 2011;69:675–89.

    Article  PubMed  Google Scholar 

  39. Holecek M. Three targets of branched-chain amino acid supplementation in the treatment of liver disease. Nutrition. 2010;26:482–90.

    Article  CAS  PubMed  Google Scholar 

  40. Román E, Torrades MT, Nadal MJ, Cárdenas G, Nieto JC, Vidal S, et al. Randomized pilot study: effects of an exercise programme and leucine supplementation in patients with cirrhosis. Dig Dis Sci. 2014;59:1966–75.

    Article  PubMed  CAS  Google Scholar 

  41. Les I, Doval E, García-Martínez R, Planas M, Cárdenas G, Gómez P, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study. Am J Gastroenterol. 2011;106:1081–8.

    Article  CAS  PubMed  Google Scholar 

  42. Als-Nielsen B, Koretz RL, Kjaergard LL, Gluud C. Branched-chain amino acids for hepatic encephalopathy. Cochrane Database Syst Rev. 2003;2003:CD001939.

    Google Scholar 

  43. Gluud LL, Dam G, Les I, Marchesini G, Borre M, Aagaard NK, et al. Branched-chain amino acids for people with hepatic encephalopathy. Cochrane Database Syst Rev. 2017;5:CD001939.

    PubMed  Google Scholar 

  44. Holeček M. Branched-chain amino acid supplementation in treatment of liver cirrhosis: updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation. Nutrition. 2017;41:80–5.

    Article  PubMed  CAS  Google Scholar 

  45. Martin P, DiMartini A, Feng S, Brown R, Fallon M. Evaluation for liver transplantation in adults: 2013 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Hepatology. 2014;59:1144–65.

    Article  PubMed  Google Scholar 

  46. Buonomo AR, Zappulo E, Scotto R, Pinchera B, Perruolo G, Formisano P, et al. Vitamin D deficiency is a risk factor for infections in patients affected by HCV-related liver cirrhosis. Int J Infect Dis. 2017;63:23–9.

    Article  CAS  PubMed  Google Scholar 

  47. Konstantakis C, Tselekouni P, Kalafateli M, Triantos C. Vitamin D deficiency in patients with liver cirrhosis. Ann Gastroenterol. 2016;29:297–306.

    PubMed  PubMed Central  Google Scholar 

  48. Kubesch A, Quenstedt L, Saleh M, Rüschenbaum S, Schwarzkopf K, Martinez Y, et al. Vitamin D deficiency is associated with hepatic decompensation and inflammation in patients with liver cirrhosis: a prospective cohort study. PLoS One. 2018;13:e0207162.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Yang F, Ren H, Gao Y, Zhu Y, Huang W. The value of severe vitamin D deficiency in predicting the mortality risk of patients with liver cirrhosis: a meta-analysis. Clin Res Hepatol Gastroenterol. 2019;43(6):722–9.

    Article  CAS  PubMed  Google Scholar 

  50. Kotlarczyk MP, Perera S, Ferchak MA, Nace DA, Resnick NM, Greenspan SL. Vitamin D deficiency is associated with functional decline and falls in frail elderly women despite supplementation. Osteoporos Int. 2017;28:1347–53.

    Article  CAS  PubMed  Google Scholar 

  51. Bruyère O, Cavalier E, Reginster J-Y. Vitamin D and osteosarcopenia: an update from epidemiological studies. Curr Opin Clin Nutr Metab Care. 2017;20:498–503.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Hirschfeld HP, Kinsella R, Duque G. Osteosarcopenia: where bone, muscle, and fat collide. Osteoporos Int. 2017;28:2781–90.

    Article  CAS  PubMed  Google Scholar 

  53. Phu S, Bani Hassan E, Vogrin S, Kirk B, Duque G. Effect of denosumab on falls, muscle strength, and function in community-dwelling older adults. J Am Geriatr Soc. 2019;67(12):2660–1.

    Article  PubMed  Google Scholar 

  54. Remelli F, Vitali A, Zurlo A, Volpato S. Vitamin D deficiency and sarcopenia in older persons. Nutrients. 2019;11:E2861.

    Article  PubMed  Google Scholar 

  55. Rudman D, Sewell CW, Ansley JD. Deficiency of carnitine in cachectic cirrhotic patients. J Clin Invest. 1977;60:716–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Shiraki M, Shimizu M, Moriwaki H, Okita K, Koike K. Carnitine dynamics and their effects on hyperammonemia in cirrhotic Japanese patients. Hepatol Res. 2017;47(4):321–327.

  57. de Sousa C, Leung NW, Chalmers RA, Peters TJ. Free and total carnitine and acylcarnitine content of plasma, urine, liver and muscle of alcoholics. Clin Sci. 1988;75:437–40.

    Article  Google Scholar 

  58. Ohara M, Ogawa K, Suda G, Kimura M, Maehara O, Shimazaki T, et al. L-Carnitine suppresses loss of skeletal muscle mass in patients with liver cirrhosis. Hepatol Commun. 2018;2:906–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hiramatsu A, Aikata H, Uchikawa S, Ohya K, Kodama K, Nishida Y, et al. Levocarnitine use is associated with improvement in sarcopenia in patients with liver cirrhosis. Hepatol Commun. 2019;3:348–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Nakanishi H, Kurosaki M, Tsuchiya K, Nakakuki N, Takada H, Matsuda S, et al. L-carnitine reduces muscle cramps in patients with cirrhosis. Clin Gastroenterol Hepatol. 2015;13:1540–3.

    Article  CAS  PubMed  Google Scholar 

  61. Malaguarnera M. Acetyl-L-carnitine in hepatic encephalopathy. Metab Brain Dis. 2013;28:193–9.

    Article  CAS  PubMed  Google Scholar 

  62. Bode JC, Hanisch P, Henning H, Koenig W, Richter FW, Bode C. Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology. 1988;8:1605–9.

    Article  CAS  PubMed  Google Scholar 

  63. Chavez-Tapia NC, Cesar-Arce A, Barrientos-Gutiérrez T, Villegas-López FA, Méndez-Sanchez N, Uribe M. A systematic review and meta-analysis of the use of oral zinc in the treatment of hepatic encephalopathy. Nutr J. 2013;12:74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Shen Y-C, Chang Y-H, Fang C-J, Lin Y-S. Zinc supplementation in patients with cirrhosis and hepatic encephalopathy: a systematic review and meta-analysis. Nutr J. 2019;18:34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H. Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther. 2010;32:1080–90.

    Article  CAS  PubMed  Google Scholar 

  66. Sengupta S, Wroblewski K, Aronsohn A, Reau N, Reddy KG, Jensen D, et al. Screening for zinc deficiency in patients with cirrhosis: when should we start? Dig Dis Sci. 2015;60:3130–5.

    Article  CAS  PubMed  Google Scholar 

  67. Bajaj JS, Salzman NH, Acharya C, Sterling RK, White MB, Gavis EA, et al. Fecal microbial transplant capsules are safe in hepatic encephalopathy: a phase 1, randomized, placebo-controlled trial. Hepatology. 2019;70:1690–703.

    Article  CAS  PubMed  Google Scholar 

  68. Ticinesi A, Lauretani F, Milani C, Nouvenne A, Tana C, Del Rio D, et al. Aging gut microbiota at the cross-road between nutrition, physical frailty, and sarcopenia: is there a gut-muscle axis? Nutrients. 2017;9:E1303.

    Article  PubMed  CAS  Google Scholar 

  69. Casula EP, Bisiacchi PS, Corrias M, Schiff S, Merkel C, Amodio P, et al. Acute hyperammonaemia induces a sustained decrease in vigilance, which is modulated by caffeine. Metab Brain Dis. 2015;30:143–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Center for Liver Diseases, University of Pittsburgh, 3471 Fifth Avenue, Suite 201, Pittsburgh, PA, 15213, USA

    Tariq Salim & Andres Duarte-Rojo

  2. Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA

    Susan A. Stark & Andres Duarte-Rojo

  3. Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA

    Andres Duarte-Rojo

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  1. Tariq Salim
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  3. Andres Duarte-Rojo
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Correspondence to Andres Duarte-Rojo.

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Dr. Duarte-Rojo reports non-financial support from Echosens, other from Mallinckrodt, other from Axcella, outside the submitted work. The other authors declare no conflicts of interest.

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Salim, T., Stark, S.A. & Duarte-Rojo, A. Food as Therapy for Frailty. Curr Hepatology Rep 19, 23–29 (2020). https://doi.org/10.1007/s11901-020-00509-x

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