The present cohort study showed that higher intake of dietary total protein and dairy protein and lower intake of animal protein were associated with reduced risk of mortality in cirrhotic patients, after fully adjustment of confounding factors such as sex, age, smoking, alcohol, BMI, energy intake, etiology, Child Pugh and MELD score.
In consistent with the findings of the present study, previous studies have shown the relationship between dietary total and vegetable protein intake and the reduction of the risk of mortality (13, 15), as well as the relationship between dietary animal protein intake and the increase of the risk of mortality (15) in various diseases. Also, replacing animal protein, especially processed red meat, with vegetable protein reduced the risk of mortality, which indicates the importance of the protein source (22). An evaluation of a large cohort study in the United States of men and women with 16 years of follow-up presented that higher intake of plant protein decreased the risk of CVD and all-cause mortality in both sexes. Also, in this study, a significant inverse relationship was observed in replacing red meat and egg protein with vegetable protein, including pasta, bread, and grains (23).
Vegetable protein may reduce systolic and diastolic blood pressure, improve lipoprotein and lipid profile and decrease insulin-like growth factor-1(IGF-1) (24–26). In agreement with our study, in a large cohort study on cirrhotic patients waiting for liver transplant, it has been reported that low protein intake was prevalent and resulted in liver disease severity and worse clinical outcomes (27). Also, it was independently associated with mortality and malnutrition (27). Sam et al. reported that protein-energy malnutrition was prevalent in cirrhotic patients and was associated with higher in-hospital mortality (28). Moreover, in another study it has been shown that in cirrhotic condition, restricted dietary protein may stimulate protein catabolism and worsen hepatic encephalopathy (29). In cirrhotic patients, protein requirement is higher than healthy population due to alterations in protein metabolism, PEM, muscle breakdown and protein-losing enteropathy caused by portal hypertension which may result in excessive intestinal protein losses (30). Several factors connected low protein intake with cirrhosis-related mortality. First, protein is an important substance in human body necessary for carrying out vital body functions. Second, infection is a major cause of death in cirrhotic patients and low protein diet impairs both humoral and cell-mediated immunity and low dietary protein causes pro-inflammatory state (31). Third, sufficient protein intake is necessary for muscle synthesis. In cirrhotic patients, glycogen reserves and synthetic capacity of liver is impaired, compensated by increased gluconeogenesis using amino acids of skeletal muscles (32).
The relationship between the dairy and vegetable protein intake and better nutritional and clinical status of cirrhotic patients has been already demonstrated (33). Consistently, in a randomizes cross-over trial, Bianchi et al. reported that in cirrhotic patients with chronic encephalopathy, vegetable protein could ameliorate nitrogen balance and mental state (34). In addition to protein, vegetables are also rich in fiber. By inducing the mass of colon bacteria, fiber increases nitrogen consumption and reduces the incidence of hepatic encephalopathy (35).
Furthermore, the low level of plasma BCAAs including valine, leucine and isoleucine, is hallmark feature of cirrhosis patients (36). Dairy and vegetable products are rich sources of BCAAs. Ruiz-Margain et al. reported that high-fiber, high-protein diet and BCAAs might increase muscle mass and prevent the increase in glucose and ammonium levels (37). Another randomized control trial on cirrhotic patients showed that BCAAs supplementation improved prognosis, quality of life, nutritional status and albumin synthesis (12). BCAAs activate mTOR signaling pathway which stimulates synthesis of muscle protein and albumin and regenerates liver cell (36).
Investigating the association of protein intake, separated by source, with the risk of cirrhosis-related mortality for the first time is one of the strengths of current cohort study. In addition, adjusting potential confounders increased the reliability of current study. The present study has limitations that should be considered, including relatively small study population, inevitable recall bias using food frequency questionnaire (FFQ) and missing of about 15% of enrolled patients.