Open-labeled Pilot Study of Cysteine-rich Whey Protein Isolate Supplementation for Nonalcoholic Steatohepatitis Patients

Taned Chitapanarux; Prasong Tienboon; Suwalee Pojchamarnwiputh; Donrawee Leelarungrayub


J Gastroenterol Hepatol. 2009;24(6):1045-1050. 

In This Article

Abstract and Introduction


Background and Aims: Glutathione (GSH) depletion contributes to liver injury and development of steatohepatitis. Undenatured cysteine-rich whey protein isolate has been clinically proven to raise GSH in several patient groups. The aim of this study was to evaluate the effect of oral supplementation with whey protein on patients with nonalcoholic steatohepatitis (NASH).
Methods: In an open-labeled clinical trial, 38 patients (18 male, 20 female; mean age 48 ± 14 years) with NASH confirmed by computed tomography measurements and liver biochemistries were given with a daily dose of 20 g whey protein isolate for 12 weeks.
Results: A significant reduction in alanine aminotransferase (ALT) (64 ± 72 vs 46 ± 36, P = 0.016) and aspartate aminotransferase (AST) (45 ± 49 vs 33 ± 18, P = 0.047) were observed. Plasma glutathione and total antioxidant capacity increased significantly at the end of study (53 ± 11 vs 68 ± 11, P < 0.05 and 1.26 ± 0.10 vs 2.03 ± 0.10, P < 0.05). Liver attenuation index improved from −13.4 ± 11.1 to −9.7 ± 13.1 (P = 0.048). Hepatic macrovesicular steatosis decreased significantly after 12 weeks of supplementation (33.82 ± 12.82 vs 30.66 ± 15.96, P = 0.046). Whey protein isolate was well tolerated. No serious adverse events were observed.
Conclusions: The results indicate that oral supplementation of cysteine-rich whey protein isolate leads to improvements in liver biochemistries, increased plasma GSH, total antioxidant capacity and reduced hepatic macrovesicular steatosis in NASH patients. The results support the role of oxidative stress in the pathogenesis of this disease.


Nonalcoholic fatty liver disease (NAFLD) is becoming a common cause of chronic liver disease in Thailand reflecting the increasing prevalence of obesity and diabetes. Nonalcoholic steatohepatitis (NASH) is part of a spectrum of NAFLD that ranges from pure fatty liver (steatosis) to steatohepatitis and cirrhosis.[1] Long-standing NASH with cirrhosis has been associated with the development of hepatocellular carcinoma.[2] The pathogenesis of NASH is not well defined. A 'two hit' hypothesis has been proposed, whereby steatosis (first hit) sensitizes the liver to a variety of metabolic injuries (second hit) that lead to necrosis, inflammation and fibrosis.[3,4] Mitochondrial dysfunction is thought to play a central role in disease progression from steatosis to cirrhosis. Increase production of reactive oxygen species and mitochondrial outer membrane permeabilization result in a cascade of events leading to inflammation, hepatocellular apoptosis, fibrogenesis and fibrosis.[5] Hepatocyte and plasma glutathione (GSH) decreased in nonalcoholic liver disease patients; whereas glutathione disulfide (GSSG) increased in these patients.[6–8] As a consequence, strategies to increase glutathione concentrations and to compensate for the oxidant-antioxidant-imbalance were brought into focus of clinical research.

There are no medical drugs approved for the treatment of NASH. However, the postulated links with factors of oxidative stress, together with the observation of glutathione depletion, provide a compelling rationale for the evaluation of treatment modalities that increase glutathione. Sufficient cysteine supply is essential for the maintenance of the glutathione pool.[9] An undenatured cysteine-rich whey protein isolate has been proven to raise glutathione levels by supplying the precursors required for intracellular glutathione synthesis. This has been demonstrated in several glutathione-deficient patient groups including those with advanced human immunodeficiency virus (HIV)-infection.[10] Consequently, a pilot, prospective clinical study was performed to determine the potential benefits of supplementation with undenatured cysteine-rich whey protein isolate in untreated patients with NASH. Hepatic steatosis was evaluated by quantitative assessment of liver-spleen attenuation differences from computed tomography and specific biochemical parameters were monitored in plasma to investigate the potential role of glutathione in patients with NASH.


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