Bob Roehr

November 09, 2010

November 9, 2010 (Boston, Massachusetts) — A 4.3% reduction in body weight and an approximate 42% reduction of triglyceride levels in subjects with nonalcoholic fatty liver disease (NAFLD) was achieved with 2 weeks of dietary intervention. Dietary restriction of carbohydrates was significantly more effective in reducing liver triglycerides than a low-calorie diet, due in part to enhanced lipid disposal by hepatic and whole-body β-oxidation.

Jeffrey D. Browning, MD, from the University of Texas Southwestern Medical Center, in Dallas, discussed his research with Medscape Medical News at The Liver Meeting 2010: American Association for the Study of Liver Diseases 61st Annual Meeting, where he presented his group's findings. Dr. Browning said basic research has shown that lipogenesis — taking a carbohydrate, breaking it down, and building it up into a fat molecule — is hyperactive in patients who have fatty liver disease.

"Normally, that should happen after a meal in the presence of insulin. Lipogenesis should go up and, as your insulin falls off, lipogenesis should go down. But in patients with fatty liver disease, it is up and it stays up, regardless of whether they have eaten or not."

His hypothesis was that in limiting carbohydrates, not only would the synthesis of new fat in the liver be limited, it would also "open up a disposal pathway for the fat that may already be there by de-inhibiting mitochondrial oxidation."

The study randomized 18 patients with NAFLD to eat either a carbohydrate-restricted (<20 g/day) or a calorie-restricted diet (1200 to 1500 kcal/day) for 2 weeks. Weight loss was similar in the low-calorie and low-carbohydrate groups (–4.0 ± 1.5 vs –4.6  ± 1.5 kg; P = .363).

Dr. Browning said they designed the study to achieve equal weight loss "so that you couldn't argue that the reason why we were seeing more fat reduction in the liver was because they had more weight loss."

They also hypothesized that there would be an increase in ketone production and the respiratory quotient (the ratio of CO2 production to O2 use). "With a respiratory quotient of 1, you are primarily burning carbohydrate as your energy source. As you go lower, toward 0.7, you are primarily burning fat."

The respiratory quotients were much different in the 2 groups, suggesting that lipogenesis was limited because of the decrease in carbohydrate intake. Both groups had an increase in ketones from baseline, but the increase was much more dramatic in those on the carbohydrate-restricted diet.

"Others have shown that if you take this diet out 6 months, there is no difference in the amount of fat that is reduced in the liver. If you take this out 6 months to a year, it probably doesn't matter what diet you're eating, as long as you are losing weight," he said.

After 6 to 12 months of weight loss, "you have kind of leveled the playing field. A lot of these metabolic consequences of fatty liver disease are probably gone by 6 months, so there is no metabolic advantage to carbohydrate restriction."

Dr. Browning said the study "was more an exercise in knowing what the underlying physiology was. Can we manipulate it in the short term? This shows that we can." It may have implications in situations where a more rapid decline in triglycerides is desirable.

"I wouldn't tell a clinician that this [diet] is better than that [diet] based on this study, but I would say, whatever works for the patient is fine," he said.

The study was conducted under an National Institutes of Health grant. Dr. Browning has disclosed no relevant financial relationships.

The Liver Meeting 2010: American Association for the Study of Liver Diseases (AASLD) 61st Annual Meeting: Abstract 630. Presented October 30, 2010.


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