Chronic liver disease (CLD) results in protein-calorie malnutrition, which can be observed in 65-90% of patients with advanced CLD 12. Between 1980-2013, 46% increase in CLD mortality was reported, especially in the low and low-middle income countries of Asia and Africa 3. Nonalcoholic fatty liver disease (NAFLD) is the most common form of CLD, ranging from steatosis to steatohepatitis, and is characterized by obesity, insulin resistance, and dyslipidemia; whereas cirrhosis is the final stage of CLD, characterized by liver structure disruption and widespread nodule formation 45. Besides unhealthy lifestyle, another reason for NAFLD prognosis is insulin resistance-induced hyperglycemia that affects macronutrient metabolism, resulting in further development of steatohepatitis, cirrhosis and hepatocellular carcinomas in worst-case scenario 6. The American Diabetes Association recommends weight loss by modifications in diet habit, focusing more on carbohydrate source, fiber, and glycemic index (GI) of the food, along with pharmacotherapy for management of CLD 7. Patients with liver disease must aim to reduce 5-10% body weight by opting a moderate carbohydrate diet (40-65% of energy), along with consumption of limited saturated and trans fat, fructose, and simple carbohydrates 48. Generally, patient with NAFLD consumes carbohydrate foods with high GI,which is associated with insulin resistance, and metabolic and liver dysfunction 9, as well as higher risk of mortality 10.The carbohydrate content of a food is measured by GI value, typically after consuming a carbohydrate containing test food relative to a carbohydrate containing reference food (glucose or white bread). The International Standards Organisation (ISO 26642-2010) has standardized the determination of GI (low, medium or high GI) of carbohydrates in foods 11. Limiting high GI diet in NAFLD patients has shown beneficial effects 9 as it elicits a low postprandial glucose response and prevents development of hepatogenous diabetes, i.e., diabetes caused by liver dysfunction in CLD patients 48.

A high protein and energy dense nutritional supplement with added branched-chain amino acids (BCAA) is designed especially for patients with CLD to maintain an adequate calorie and protein intake. The supplement may help individuals with CLD to manage their postprandial glucose levels, and to improve immunity. A cross-over randomized controlled study was designed to estimate the GI value of this liver nutritional supplement in healthy individuals.

This study was conducted using internationally recognized GI protocol by FAO/WHO, recommended guidelines by International dietary carbohydrate task force for GI methodology 12, and International Standards Organisation (ISO 26642-2010) 11which have been validated and published 13. The procedure used in this study was in accordance with international standards for conducting ethical research with humans and was approved by the institutional ethics committee of Madras Diabetes Research Foundation (MDRF), Chennai, India. The study was registered in the clinical trial registry of India, CTRI/2021/08/035929, and designed according to the Consolidated Standards of Reporting Trials (CONSORT). Informed consent was obtained from all study participants.

The growing incidence of CLD all over the world stresses the urgent need for dietary and lifestyle modifications. The knowledge of GI of a food is necessary to make healthy food choices. There are evidences, suggesting beneficial role of low GI diet in overweight/obese patients 14, and patients with NAFLD 89. As far as we are concerned this is the first study to assess the GI value of a newly launched liver nutritional supplement in healthy individuals, which is a protein and energy dense food with added BCAA, vitamins and minerals. In addition, change in blood glucose level after consumption of this food relative to consumption of glucose was also compared. The GI of this n utritional supplement was estimated as 11.4 ± 2.4 which falls within the ‘low GI category’. Moreover, there was a lower blood sugar response with this supplement, compared to the reference food, throughout the postprandial period.

The association between CLD and diabetes mellitus is known since long, and consumption of low GI diet helps to control CLD-induced hepatogenous diabetes and protein calorie malnutrition 15. In our previous study, we have assessed the GI and glycemic response of a plant-based supplement, and found that low GI diet has improved satiety and can be included in the diet to reduce the postprandial glycemic response in overweight and obese people 14. Recently, a significant reduction in hepatic mass in individuals without NAFLD is also reported with low GI diet 9. In a previous randomized cross-over study, healthy males have participated in two 7 day high GI and low GI diets, separated by a 4 week wash-out period. In this study, an increase in fasted fat fractions after high GI diet and a decrease in fasted fat fractions after low GI diet were observed compared to baseline. For the low GI diet, significant reduction in fat fractions at 360 minutes after test meal was also noticed 16.

In a randomized, double-blind, parallel design diet intervention study, the effects of a low-fat/ low saturated fat/ low GI diet (LSAT) was compared to a high-fat/ high saturated fat/ low GI diet in older adults over a 4 week period. Compared to baseline, LSAT showed significant reduction in liver fat percentage 17. The findings were also consistent with another cross-sectional study, in which a strong correlation between higher GI foods and high-grade liver stenosis, particularly among individuals with insulin resistance was recorded 18. Furthermore, the liver biomarker, alanine transaminase was reported to be significantly improved in obese individuals with type 2 diabetes after consuming low GI diet along with a modified Mediterranean diet 19.

Patients with CLD have a tendency to suffer from fat-soluble vitamin deficits, early recognition of which is essential to reduce the chances of infection, in-hospital mortality and to improve the liver function 2. Therefore, modifications in the diet to compensate the nutrient deficiency and to make healthy lifestyle choices are highly recommended in order to control plasma glucose level and CLD prognosis. The consumption of low GI foods may have a beneficial impact on the society as this can help to enhance the quality of life, health and well-being of the patient by reducing the burden of disease progression to advanced liver diseases. This in turn emphasizes the need for developing low GI nutritional supplement with ingredients, beneficial for liver health.

Mean GI of the liver nutritional supplement was estimated as 11.4 ± 2.4 which is below 55, hence has a low GI. The supplement is high in protein and is energy dense, it has slower and more sustained blood glucose response compared to glucose. Therefore, the supplement can be used as an adjuvant to treatment in patients with CLD to prevent CLD-associated metabolic complications and improve overall health outcomes and quality of life.

This research was funded by Dr. Reddy’s Laboratories Ltd.

Institutional review board statement: The study was reviewed and approved by the institutional ethics committee of Madras Diabetes Research Foundation, Chennai, India.

Clinical trial registration statement: The study was registered in the clinical trial registry of India. The registration identification number is CTRI/2021/08/035929.

Informed consent statement: Prior to the study, informed consent was obtained from all study participants.