This study aimed to investigate the effects of LES supplementation (lotus-root starch) for 2 weeks on fasting resting expenditure and nutrient oxidation in adults with ACLF due to Hepatitis B infection. The results show that daily consumption of a CHO-predominant LES for 14 days significantly increased carbohydrate oxidation and reduced fat oxidation in the fasted state in normo-metabolic adult patients with ACLF due to Hepatitis B infection. This was particularly evident in patients with MELD scores less than 30, indicating that LES supplementation using a CHO-based (lotus starch) LES may be an effective strategy to minimize the utilization of lean body stores for energy in the fasted state in patients with milder liver disease. This coincided with increases in fasting REE for patients with MELD scores less than 30, suggesting that alteration in substrate utilization with an CHO-predominant LES may have lead to improvements or stabilization in overall lean body mass in adults with ACLF.
Many studies have examined the efficacy of nutrient supplementation in patients with liver cirrhosis as the vehicle to improve overall nutritional status as the prevalence of protein-energy malnutrition is significantly high in this population.29 Most of these studies have focused on BCAA supplementation and the associated improvements in the quality of life and overall nitrogen balance7, 12, 14, 15, 16, 17, 18, 30, 31, 32, 33, 34, 35 that have been associated with the use of BCAA supplements in adults with liver disease. However, issues related to lack of long-term adherence to BCAA supplementation due to gastrointestinal upset have made long-term studies challenging.7, 33
More recently a stronger focus has been on the use of late-evening snacks (LES) as a method to minimize utilization of tissue stores for energy needs in the fasted state in patients with chronic liver disease.7, 14, 15, 16, 17, 18, 19, 36 Nocturnal energy supplementation could potentially be useful to correct abnormal fuel metabolism and to prevent malnutrition in patients with liver cirrhosis.17 Yamanaka-Okumura et al.13 showed that a carbohydrate-based LES with (rice ball) for 7 days resulted in significant increases in fasting RQs in adults with liver cirrhosis. Similar findings have also been shown with the use of BCAA-enriched LES in adults with chronic liver disease, but few of these studies have been done in patients with ACLF or have examined the effects of the BCAA in isolation of other macronutrients.7, 12, 14, 15 Hence, it is unclear the extent to which the actual BCAA by themselves contribute to improvements in overall nutrient utilization in the fasted state in patients with chronic liver or whether a combination of both carbohydrate and BCAA in an LES contributes to overall changes in fasting nutrient oxidation and energy metabolism.15 However, it is clear that offering an LES as an alternative to simply increasing total energy intake during the day has the greatest benefits.7, 12, 14, 34
Many studies have shown that cirrhotic patients have altered nutrient and energy metabolism, which can contribute to the increased risk for malnutrition and also seriously affect their prognosis.34, 35 Chun-Lei Fan9 showed that adults with chronic liver disease typically have significantly higher rates of fat oxidation and significantly lower rates of glucose oxidation resulting in increased utilization of body stores (lean body mass and fat mass). For patients with ACLF, acute decompensation in liver function can further exacerbate this issue, contributing to increased nutritional risk. The use of a carbohydrate-based nutritional module that is slowly digested and absorbed potentially may compensate for this deterioration in liver function and there by promoting increased utilization of this substrate for energy needs in the fasted state. The reason for this phenomenon may be related to the low glycemic index of the source of carbohydrate used within this study (∼33).21 Foods with low glycemic index are typically absorbed more slowly overnight, which may have resulted in increased carbohydrate utilization (higher fasting RQ) and a reduction in fat and protein mobilization from the adipocyte and lean tissue. Overall this could potentially minimize the extent to which protein-energy malnutrition occurs in patients with mild-moderate liver disease. Indeed, our data suggest that those with MELD scores less than 30 are more responsive to changes in nutrient oxidation with a CHO-predominant LES than those with MELD scores above 30, where little or no changes in fasting RQ/nutrient oxidation were observed. Therefore, it is possible that a CHO-predominant LES may prove less effective as a nutrition support approach to prevent protein-energy malnutrition in ACLF patients with more severe disease. This may be due in part to the potential for more severe lean body mass depletion in those with more severe disease.
The efficacy of a CHO-predominant LES vs a combined CHO-protein LES snack as a nutritional support approach to correct protein-energy malnutrition may also be related to the extent of lean body mass depletion experienced by ACLF patients, particularly in those with severe disease and/or those individuals with hypermetabolism. These factors may result in increased needs for both nocturnal sources of protein and CHO-predominant LES.5 In this study, only increases in REE (on an absolute kcal basis and on a per kg body weight basis) were observed in the patients with milder liver disease (MELD scores⩽30) supplemented with the LES. This coincided with small gains in body weight in this group which may reflect increases in over all lean body mass and overall nutritional status, resulting in modest increases in REE (from 83.9 to 105% predicted). However, it is unclear whether changing the macronutrient composition or dose of the LES would confer greater changes in lean body mass, improvements in overall nutritional status, REE and/or substrate oxidation in ACLF patients with more severe disease. Two studies showed that higher energy intakes of an LES (700 kcal vs 200 kcal) resulted in significantly higher gains in lean body mass accumulation in adults with chronic liver disease over 1 year of supplementation.13, 37 Other studies have also shown that LES that contain both protein (in the form of BCAA) and varying levels of CHO and fat have also shown to be equally as effective at promoting positive changes in nutrient utilization, but inconsistent findings have been found in terms of the impact of this on overall REE.12, 14, 34 More work needs to be done to confirm the efficacy of varying energy and macronutrient composition of LES in ACLF patients on substrate utilization and REE over a spectrum of liver disease severity.
Limitations in this study design include the smaller sample size which made it difficult to determine the efficacy of LES supplementation on nocturnal CHO utilization based on liver disease severity (MELD scores above and below 30). A conferred strength is that the population studied was relatively homogeneous (Hepatitis B), was not hypermetabolic, and changes in substrate utilization were measured using validated methodologies, demonstrating that the addition of a relatively small CHO-based LES was associated with favorable improvements in fasting nutrient utilization. In addition, none of the patients experienced any adverse side effects. Lotus-root starch is a common traditional food in China, which is easily cooked and can be used for long-term daily consumption for patients without any socioeconomic constraints as it is inexpensive and an affordable alternative compared with other nutrient modules. Lotus-root starch has a significantly lower glycemic index than most other sources of wheat or rice starches, and hence offers the opportunity to prolong postprandial euglycemia.21 It also potentially avoids the adverse side effects of other modules like the BCAA: gastrointestinal upset and the potential for hypoglycemia.7, 38 This is particularly important in a population that can experience significant and rapid reductions in hepatic reserve and function. Similar benefits have been observed when LES have been combined with α-glucosidase inhibitors in patients with liver cirrhosis.39 Studying the postprandial glucose response to the LES using a glucose tolerance test) would have added conferred strength to understanding the contribution of the LES to overall postprandial carbohydrate utilization; but unfortunately this analysis was not performed.
One interesting finding was a significant increase in cholinesterase, a marker of hepatic reserve, significantly increased in the LES supplemented group. Although the use of an LES supplement may have been contributing factor in this, it is more likely that overall medical management (antiviral and anti-infective therapy) are more likely to have the major factor because we did not observe any major differences in overall liver function between the two groups after 2 weeks.
In conclusion, the ingestion of a LES carbohydrate module (lotus-root starch) in normo-metabolic ACLF patients with mild-moderate disease severity, was associated with increased carbohydrate utilization and reductions in fat utilization in the fasted stated. This may be due to the lower GI of the carbohydrate module resulting in prolonged postprandial delivery of CHO into the blood stream following nocturnal consumption, but further investigation is required to confirm this finding. Although these findings should be validated in larger prospective trials of longer study duration, these results advocate the necessity of nocturnal carbohydrate supplementation in the management of patients with ACLF.