NASH, the second stage of non-alcoholic fatty liver disease (NAFLD) is characterised by inflammatory changes which can further progress to fibrosis, cirrhosis and even liver cancer. The overconsumption of certain carbohydrates (particularly fructose) and some types of fats, together with lack of exercise are recognised as contributory to the prevalence of the disease. NHS statistics suggest that NASH may be present in up to 5% of the UK population.
The amino acid l-glutamine has shown potential preventive benefits for NAFLD in previous animal studies. However, this is the first study that has shown a protective effect in pre-existing NASH, reported the research team, a collaboration between the Friedrich-Schiller University, Jena, Germany and the University of Vienna.
“Our data suggest that oral supplementation of glutamine at pharmacological doses prevents the progression of NAFLD in mice with pre-existing NASH,” wrote first author Cathrin Sellmann from Institute of Nutritional Sciences at Friedrich Schiller University.
“These findings are in line with previous findings of our group and others showing that the protective effects of supplementation with glutamine on the development of NAFLD were associated with a marked protection against hepatic steatosis and inflammation.”
If validated in humans, the possibility of l-glutamine as a therapy could be significant. Currently, reversal of NASH is dependent primarily on lifestyle and dietary changes.
The study used female mice (known to be more susceptible to fructose induced NAFLD than males). Mice were fed for 8 weeks with isocaloric daily intakes of either a Western Style Diet (WSD) (60 energy % (E%) from carbohydrates, 25 E% from fat, 15 E% from protein, including 50% by weight fructose and 0.16% by weight cholesterol; or a control diet (69% of energy (E%) from carbohydrates, 12 E% from fat, 19 E% from protein).
The scientists analysed the blood and examined the liver histology of some of the mice (from each group) after eight weeks.
The remaining mice in the control and WSD groups were further divided, with some mice each in original groups being supplemented with l-glutamine at a dose of 2.1 grams per kilogram (g/kg) of body weight. The mice were then fed as before, WSD or control diet for a further 5 weeks.
Further blood tests were performed including triglycerides, markers of inflammation and lipid peroxidation, glucose tolerance and liver enzymes. Liver histology was again examined to determine progression of liver disease.
“Mice developed marked steatosis with inflammation beginning after just 8 weeks of feeding them the WSD,” wrote the researchers.
The scientists also that found markers of inflammation were significantly higher in the livers of the WSD-fed mice, whereas in those fed WSD + glutamine, the markers were similar to controls.
The beneficial effects of l-glutamine are associated with lower levels of lipid peroxidation in the liver, rather any improved in glucose tolerance, the researchers suggested. .
“However, the molecular mechanisms underlying the therapeutic effect of glutamine remain to be determined. Furthermore, future studies will need to assess if similar beneficial effects of oral glutamine supplementation are also found in [human] patients with NAFLD,” they concluded.
It should be noted that the safety of pharmacological doses of glutamine in humans (equivalent to the 2.1 g/kg given to the mice) has not been established.
Source: Journal of Nutrition
Volume 147, issue 11, pp 2041-2049 DOI: 10.3945/jn.117.253815
“Oral Supplementation of Glutamine Attenuates the Progression of Nonalcoholic Steatohepatitis in C57BL/6J Mice”
Authors: Cathrin Sellmann, Anja Baumann, Annette Brandt, Cheng Jun Jin, Anika Nier, and Ina Bergheim.