DISTRIBUTION OF CALORIE INTAKE
The distribution of calorie intake throughout the day has also been studied. It has been proposed that eating a late evening snack could alleviate the shift towards lipid oxidation by reducing the length of time a patient fasts overnight. Indeed, a late evening meal has been shown to improve the nitrogen balance57 and raise the nonprotein respiratory quotient.58 A typical recommendation for patients with advanced liver disease is to consume four to five small meals per day, as well as a late evening snack.
Supplementation with branched-chain amino acids
The usefulness of branched-chain amino acid (BCAA) supplementation in patients with cirrhosis has long been debated. It was proposed that depletion of BCAAs, as seen in many patients with advanced liver disease, might promote the development of hepatic encephalopathy by enhancing the passage of aromatic amino acids across the blood–brain barrier, resulting in the synthesis of false neurotransmitters. For this reason, it was hypothesized that BCAA supplementation might improve hepatic encephalopathy. Early investigations, therefore, focused on BCAAs as a potential treatment for hepatic encephalopathy. Although some controlled trials showed no benefit of BCAAs with respect to mental function,59 several trials showed a significant improvement in hepatic encephalopathy with BCAA treatment.60, 61 A 2003 review of 11 randomized trials concluded that BCAAs improve hepatic encephalopathy, particularly when administered enterally to patients with chronic encephalopathy.62
Although there are conflicting data, there is more evidence of the beneficial effects of BCAAs to support their use in the treatment of malnutrition in patients with advanced cirrhosis. Marchesini et al. performed a multicenter, randomized trial examining the role of oral BCAA supplementation in patients with advanced liver disease.63 The trial consisted of 174 patients with advanced cirrhosis who received 1 year of nutritional supplementation with BCAAs, lactoalbumin, or maltodextrins. BCAA administration was advantageous with regard to rates of mortality, progression of liver failure, and hospital admission. The most significant limitation that the investigators found was poor compliance with the BCAA-enriched diet; in the BCAA group, 15% of patients did not complete the treatment course. Poor compliance was attributed to poor palatability of the BCAA supplement. A recent multicenter, randomized, nutrient-intake-controlled trial demonstrated that oral supplementation with BCAAs for 2 years improved survival, serum albumin concentration, and quality of life in patients with decompensated cirrhosis.64
Recent studies advocate the use of nocturnal BCAA administration.65 It is believed that BCAAs that are consumed during the day are primarily used as a source of energy for physical exercise, whereas when administered at night, BCAAs might be preferentially used for protein synthesis.